title stringlengths 0 1.13k | abstract stringlengths 1 15.7k | PMID int64 22 36.5M |
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Anemia management in peritoneal dialysis patients: can an iron supplement maintain a normal transferrin saturation and hemoglobin level? | The primary cause of anemia in dialysis patients is inadequate production of erythropoietin (EPO) by the dysfunctional kidneys. The EPO circulates in plasma and acts on erythroid progenitor cells in the bone marrow to produce red blood cells (RBCs). At the same time, chronic inflammatory diseases reduce the release of iron from storage sites, resulting in low transferrin saturation (Fe+ sat%). Anemia can cause fatigue and heart problems. Two main blood tests measure anemia: hemoglobin (Hb) measures the oxygen-carrying protein in RBCs, and Fe+ sat% measures Fe+ status in the bloodstream. The goal of anemia management is to maintain Hb levels at 11 - 12 g/dL and Fe+ sat% above 20%. | 18,986,010 |
Peritoneal dialysis adequacy: not just small-solute clearance. | Two indices of small-solute clearance, Kt/V urea and creatinine clearance, are widely used as markers of peritoneal dialysis (PD) adequacy. It has become clear, however, that increasing the small-solute clearance above a minimum level does not result in improved long-term PD outcomes. Several other factors may affect optimal dialysis outcome. These include, but are not limited to, ultrafiltration, inflammation, malnutrition, and mineral metabolism. In the present article, we briefly review data regarding the relationships between the foregoing factors and survival on PD. | 18,986,011 |
An ergonomic evaluation of a call center performed by disabled agents. | Potential ergonomic hazards for 27 disabled call center agents engaged in computer-telephone interactive tasks were evaluated for possible associations between the task behaviors and work-related disorders. Data included task description, 300 samples of performance, a questionnaire on workstation design, body-part discomfort rating, perceived stress, potential job stressors, and direct measurement of environmental factors. Analysis indicated agents were frequently exposed to prolonged static sitting and repetitive movements, together with unsupported back and flexed neck, causing musculoskeletal discomforts. Visual fatigue (85.2% of agents), discomfort of ears (66.7%), and musculoskeletal discomforts (59.3%) were the most pronounced and prevalent complaints after prolonged working. 17 of 27 agents described job pressure as high or very high, and dealing with difficult customers and trying to fulfill the customers' needs within the time standard were main stressors. Further work on surrounding noise, earphone use, possible hearing loss of experienced agents, training programs, feasible solutions for visual fatigue, musculoskeletal symptoms, and psychosocial stress should be conducted. | 18,986,032 |
Development of catching by children in kindergarten to grade 8: a multicohort longitudinal study. | The purpose of this study was to examine developmental change associated with catching by children in Grades Kindergarten through 8. Children's performance was tested on the Catching Subtest of the Ohio State University Scale of Intra Gross Motor Assessment (OSU-SIGMA). More precisely, four cohorts of boys and girls in Grades K-8 (N = 340) from 1992 to 2000: in 1992 Grades K-8, in 1994 Grades 2-8, in 1996 Grades 4-8, and in 1998 Grades 6-8. In 2000, the original Kindergarten cohort was tested again. Data, analyzed by hierarchical nonlinear modeling, yielded significant differences in mean initial status (intercept) of all three cohorts, in mean growth rate (slope) for the K-8 cohort only, in initial status of the K-8 cohort, and for participants in baseball and softball. | 18,986,040 |
Voluntary visual attention and phenomenal line length. | In 1956, Fraisse, et al. reported subjects judged that lines were longer when voluntary attention was focused on the lines than when attention was distracted from the lines. In the many attempts to repeat these results, none has ascertained whether attention on reported line length was a phenomenal effect. In the present study, 46 subjects were shown as stimuli pairs of horizontal or vertical briefly flashed lines with a fixation cross placed equidistant between the lines but far from each one. A change in color of one arm of the cross was used as a cue to focus subjects' voluntary attention on one line. Analysis showed attention increased the judged length of attended lines. Since this effect of attention also occurred when subjects were absolutely certain they saw the stimulus lines differed in length, this effect indicates that attention increased the phenomenal length of the attended lines. This lengthening was quite small: it involved a maximum mean increase of about .15 in the probability of the comparative response that the attended line was longer. This effect occurred in the horizontal dimension and was almost absent in the vertical dimension. In agreement with data indicating that flashed lines expand phenomenally by activating motion detectors and that focused attention makes neural motion responses increase in amplitude, the present results suggest that focused attention makes attended lines look longer because it makes these lines expand phenomenally more rapidly. | 18,986,054 |
[Chemical and microbiological aspects of the quantitative analysis of amphotericin B]. | Amphotericin B can be determined by chemical (HPLC, spectrophotometry) and microbiological (bioassay) methods. The utilization of both during a stability test can give more detailed information about the activity and concentration change of amphotericin B solutions. Previously published HPLC methods do not lay stress on the separation of by-constituents present in the substance. We have also observed that the bioassay conditions described in the Ph. Eur. 6. are not suitable for the measurement of concentration change experienced during a stability test. The aim of our study was to optimize the chemical and microbiological methods. We have improved the eluent system based on earlier HPLC methods for the separation of the main heptaene and the minor tetraene by-constituents in Fungizone (Bristol-Myers Squibb). The most optimal bioassay conditions were determined where a relatively wide concentration range can be measured. With the improved methods both chemical and microbiological changes can be more accurately measured in our future stability tests. | 18,986,086 |
Prediction of activation energies for aromatic oxidation by cytochrome P450. | We have estimated the activation energy for aromatic oxidation by compound I in cytochrome P450 for a diverse set of 17 substrates using state-of-the-art density functional theory (B3LYP) with large basis sets. The activation energies vary from 60 to 87 kJ/mol. We then test if these results can be reproduced by computationally less demanding methods. The best methods (a B3LYP calculation of the activation energy of a methoxy-radical model or a partial least-squares model of the semiempirical AM1 bond dissociation energies and spin densities of the tetrahedral intermediate for both a hydroxyl-cation and a hydroxyl-radical model) give correlations with r(2) of 0.8 and mean absolute deviations of 3 kJ/mol. Finally, we apply these simpler methods on several sets of reactions for which experimental data are available and show that we can predict the reactive sites by combining calculations of the activation energies with the solvent-accessible surface area of each site. | 18,986,131 |
Single peptide assembly onto a 1.5 nm Au surface via a histidine tag. | Nanoparticle surfaces functionalized with proteins or other biomolecules provide a mechanism for interfacing the unique properties of nanomaterials with biological samples. In most of these studies, the biomolecule is conjugated to a gold nanoparticles (AuNP) surface through the thiol group of native or introduced cysteine residues. Here we demonstrate the direct attachment of a hexa-histidine tagged (His(6)) peptide to a 1.5 nm AuNP. Binding occurs via a specific interaction between the Ne of the His imidazole, forming a 1:1 stoichiometric complex. Given the widespread use of histidine tags in producing recombinant proteins, this approach promises to expand the applications of AuNP in biological applications. | 18,986,142 |
New cationic and zwitterionic Cp*M(kappa2-P,S) complexes (M = Rh, Ir): divergent reactivity pathways arising from alternative modes of ancillary ligand participation in substrate activation. | Treatment of 0.5 equiv of [Cp*IrCl(2)](2) with 1/3-P(i)Pr(2)-2-S(t)Bu-indene afforded Cp*Ir(Cl)(kappa(2)-3-P(i)Pr(2)-2-S-indene) (1) in 95% yield (Cp* = eta(5)-C(5)Me(5)). Addition of AgOTf or LiB(C(6)F(5))(4) x 2.5 OEt(2) to 1 gave [Cp*Ir(kappa(2)-3-P(i)Pr(2)-2-S-indene)](+)X(-) ([2](+)X(-); X = OTf, 78%; X = B(C(6)F(5))(4), 82%), which represent the first examples of isolable coordinatively unsaturated [Cp'Ir(kappa(2)-P,S)](+)X(-) complexes. Exposure of [2](+)OTf(-) to CO afforded [2 x CO](+)OTf(-) in 91% yield, while treatment of [2](+)B(C(6)F(5))(4)(-) with PMe(3) generated [2 x PMe(3)](+)B(C(6)F(5))(4)(-) in 94% yield. Treatment of 1 with K(2)CO(3) in CH(3)CN allowed for the isolation of the unusual adduct 3 x CH(3)CN (41% isolated yield), in which the CH(3)CN bridges the Lewis acidic Cp*Ir and Lewis basic indenide fragments of the targeted coordinatively unsaturated zwitterion Cp*Ir(kappa(2)-3-P(i)Pr(2)-2-S-indenide) (3). In contrast to the formation of [2 x CO](+)OTf(-), exposure of 3 x CH(3)CN to CO did not afford 3 x CO; instead, a clean 1:1 mixture of (kappa(2)-3-P(i)Pr(2)-2-S-indene)Ir(CO)(2) (4) and 1,2,3,4-tetramethylfulvene was generated. Treatment of [2](+)OTf(-) with Ph(2)SiH(2) resulted in the net loss of Ph(2)Si(OTf)H to give Cp*Ir(H)(kappa(2)-3-P(i)Pr(2)-2-S-indene) (5) in 44% yield. In contrast, treatment of [2](+)B(C(6)F(5))(4)(-) with Ph(2)SiH(2) or PhSiH(3) proceeded via H-Si addition across Ir-S to give the corresponding [Cp*Ir(H)(kappa(2)-3-P(i)Pr(2)-2-S(SiHPhX)-indene)](+)B(C(6)F(5))(4)(-) complexes 6a (X = Ph, 68%) or 6b (X = H, 77%), which feature a newly established S-Si linkage. Compound 6a was observed to effect net C-O bond cleavage in diethyl ether with net loss of Ph(2)Si(OEt)H, affording [Cp*Ir(H)(kappa(2)-3-P(i)Pr(2)-2-SEt-indene)](+)B(C(6)F(5))(4)(-) (7) in 77% yield. Furthermore, 6a proved capable of transferring Ph(2)SiH(2) to acetophenone, with concomitant regeneration of [2](+)B(C(6)F(5))(4)(-); however, [2](+)X(-) did not prove to be effective ketone hydrosilylation catalysts. Treatment of 1/3-P(i)Pr(2)-2-S(t)Bu-indene with 0.5 equiv of [Cp*RhCl(2)](2) gave Cp*Rh(Cl)(kappa(2)-3-P(i)Pr(2)-2-S-indene) (8) in 94% yield. Combination of 8 and LiB(C(6)F(5))(4) x 2.5 Et(2)O produced the coordinatively unsaturated cation [Cp*Rh(kappa(2)-3-P(i)Pr(2)-2-S-indene)](+)B(C(6)F(5))(4)(-) ([9](+)B(C(6)F(5))(4)(-)), which was transformed into [Cp*Rh(H)(kappa(2)-3-P(i)Pr(2)-2-S(SiHPh(2))-indene)](+)B(C(6)F(5))(4)(-) (10) via net H-Si addition of Ph(2)SiH(2) to Rh-S. Unlike [2](+)X(-), complex [9](+)B(C(6)F(5))(4)(-) was shown to be an effective catalyst for ketone hydrosilylation. Treatment of 3 x CH(3)CN with Ph(2)SiH(2) resulted in the loss of CH(3)CN, along with the formation of Cp*Ir(H)(kappa(2)-3-P(i)Pr(2)-2-S-(1-diphenylsilylindene)) (11) (64% isolated yield) as a mixture of diastereomers. The formation of 11 corresponds to heterolytic H-Si bond activation, involving net addition of H(-) and Ph(2)HSi(+) fragments to Ir and indenide in the unobserved zwitterion 3. Crystallographic data are provided for 1, [2 x CO](+)OTf(-), 3 x CH(3)CN, 7, and 11. Collectively, these results demonstrate the versatility of donor-functionalized indene ancillary ligands in allowing for the selection of divergent metal-ligand cooperativity pathways (simply by ancillary ligand deprotonation) in the activation of small molecule substrates. | 18,986,145 |
Apple juice clarification by immobilized pectolytic enzymes in packed or fluidized bed reactors. | The catalytic behavior of a mixture of pectic enzymes, covalently immobilized on different supports (glass microspheres, nylon 6/6 pellets, and PAN beads), was analyzed with a pectin aqueous solution that simulates apple juice. The following parameters were investigated: the rate constant at which pectin hydrolysis is conducted, the time (tau(50)) in which the reduction of 50% of the initial viscosity is reached, and the time (tau(comp,dep)) required to obtain complete depectinization. The best catalytic system was proven to be PAN beads, and their pH and temperature behavior were determined. The yields of two bed reactors, packed or fluidized, using the catalytic PAN beads, were compared to the circulation flow rate of real apple juice. The experimental conditions were as follows: pH 4.0, T = 50 degrees C, and beads volume = 20 cm(3). The initial pectin concentration was the one that was present in our apple juice sample. No differences were observed at low circulation rates, while at higher recirculation rates, the time required to obtain complete pectin hydrolysis into the fluidized reactor was found to be 0.25 times smaller than in the packed bed reactor: 131 min for the packed reactors and 41 min for the fluidized reactors. | 18,986,151 |
Sequential organocatalyzed Michael addition/[3 + 2]-heterocyclization for the stereoselective synthesis of fused-isoxazoline precursors of enantiopure cyclopentanoids. | We propose an asymmetric synthesis of functionalized cyclopentanoids bearing up to four stereogenic centers from easily accessible nitroalkenes and unsaturated aldehydes. The overall sequence includes an enantioselective organocatalytic Michael addition and a [3 + 2]-heterocyclization between an in situ generated silylnitronate and the unactivated double bond. Finally, the fused isoxazoline can be further transformed to various cyclopentanoids. | 18,986,156 |
Molecular bases for the recognition of short peptide substrates and cysteine-directed modifications of human insulin-degrading enzyme. | Insulin degrading enzyme (IDE) utilizes a large catalytic chamber to selectively bind and degrade peptide substrates such as insulin and amyloid beta (Abeta). Tight interactions with substrates occur at an exosite located approximately 30 A away from the catalytic center that anchors the N-terminus of substrates to facilitate binding and subsequent cleavages at the catalytic site. However, IDE also degrades peptide substrates that are too short to occupy both the catalytic site and the exosite simultaneously. Here, we use kinins as a model system to address the kinetics and regulation of human IDE with short peptides. IDE specifically degrades bradykinin and kallidin at the Pro/Phe site. A 1.9 A crystal structure of bradykinin-bound IDE reveals the binding of bradykinin to the exosite and not to the catalytic site. In agreement with observed high K(m) values, this suggests low affinity of bradykinin for IDE. This structure also provides the molecular basis on how the binding of short peptides at the exosite could regulate substrate recognition. We also found that human IDE is potently inhibited by physiologically relevant concentrations of S-nitrosylation and oxidation agents. Cysteine-directed modifications play a key role, since an IDE mutant devoid of all 13 cysteines is insensitive to the inhibition by S-nitrosoglutathione, hydrogen peroxide, or N-ethylmaleimide. Specifically, cysteine 819 of human IDE is located inside the catalytic chamber pointing toward an extended hydrophobic pocket and is critical for the inactivation. Thiol-directed modification of this residue likely causes local structural perturbation to reduce substrate binding and catalysis. | 18,986,166 |
Cationic copolymer-mediated DNA immobilization: interfacial structure and composition as determined by ellipsometry, dual polarization interferometry, and neutron reflection. | DNA immobilization onto support surfaces is required in biotechnological applications such as microarrays and gene delivery. This important interfacial molecular process can be mediated from a preadsobred cationic polymer. There is, however, a lack of understanding over the control of the interfacial composition and structural distribution of the DNA immobilized. We have used a combined approach of spectroscopic ellipsometry (SE), dual polarization interferometry (DPI) and neutron reflection (NR) to determine the interfacial polymer adsorption and the subsequent DNA binding. Cationic diblock copolymers incorporating 30 phosphorylcholine (PC) groups and different diethylaminoethyl groups, referred to as MPC30-DEAn, were chosen because of their well-defined molecular architecture. While our studies revealed different effects of surface charge and hydrophobicity, the amount of copolymers adsorbed on both model surfaces showed a broad trend of increase with solution pH, indicating a strong effect arising from pH-dependent charge density on the copolymers. In contrast, the copolymer structure and solution concentration showed a weak effect under the conditions studied. The subsequent DNA binding at pH 7 showed that on both surfaces the amount of DNA immobilized followed an approximate 1:1 charge interaction for all different DNA samples studied, irrespective of single or double strand, or different DNA size, indicating the dominant effect of electrostatic interaction between the two species. Both DPI and NR revealed consistent thickness increase upon DNA binding. Furthermore, with increasing DNA size, the interfacial layer became much thicker, and charge interaction drove more extensive interfacial mixing between the two species. Our results show that the amount of DNA immobilized is controlled by the amount of cationic copolymer preadsorbed that is in turn controlled by the solution pH and surface chemistry but that is barely affected by the type and concentration of DNA or cationic copolymer. | 18,986,183 |
Using a two-step hydride transfer to achieve 1,4-reduction in the catalytic hydrogenation of an acyl pyridinium cation. | The stoichiometric reduction of N-carbophenoxypyridinium tetraphenylborate (6) by CpRu(P-P)H (Cp = eta(5)-cyclopentadienyl; P-P = dppe, 1,2-bis(diphenylphosphino)ethane, or dppf, 1,1'-bis(diphenylphosphino)ferrocene), and Cp*Ru(P-P)H (Cp* = eta(5)-pentamethylcyclopentadienyl; P-P = dppe) gives mixtures of 1,2- and 1,4-dihydropyridines. The stoichiometric reduction of 6 by Cp*Ru(dppf)H (5) gives only the 1,4-dihydropyridine, and 5 catalyzes the exclusive formation of the 1,4-dihydropyridine from 6, H(2), and 2,2,6,6-tetramethylpiperidine. In the stoichiometric reductions, the ratio of 1,4 to 1,2 product increases as the Ru hydrides become better one-electron reductants, suggesting that the 1,4 product arises from a two-step (e(-)/H(*)) hydride transfer. Calculations at the UB3LYP/6-311++G(3df,3pd)//UB3LYP/6-31G* level support this hypothesis, indicating that the spin density in the N-carbophenoxypyridinium radical (13) resides primarily at C4, while the positive charge in 6 resides primarily at C2 and C6. The isomeric dihydropyridines thus result from the operation of different mechanisms: the 1,2 product from a single-step H(-) transfer and the 1,4 product from a two-step (e(-)/H(*)) transfer. | 18,986,202 |
Network hubs buffer environmental variation in Saccharomyces cerevisiae. | Regulatory and developmental systems produce phenotypes that are robust to environmental and genetic variation. A gene product that normally contributes to this robustness is termed a phenotypic capacitor. When a phenotypic capacitor fails, for example when challenged by a harsh environment or mutation, the system becomes less robust and thus produces greater phenotypic variation. A functional phenotypic capacitor provides a mechanism by which hidden polymorphism can accumulate, whereas its failure provides a mechanism by which evolutionary change might be promoted. The primary example to date of a phenotypic capacitor is Hsp90, a molecular chaperone that targets a large set of signal transduction proteins. In both Drosophila and Arabidopsis, compromised Hsp90 function results in pleiotropic phenotypic effects dependent on the underlying genotype. For some traits, Hsp90 also appears to buffer stochastic variation, yet the relationship between environmental and genetic buffering remains an important unresolved question. We previously used simulations of knockout mutations in transcriptional networks to predict that many gene products would act as phenotypic capacitors. To test this prediction, we use high-throughput morphological phenotyping of individual yeast cells from single-gene deletion strains to identify gene products that buffer environmental variation in Saccharomyces cerevisiae. We find more than 300 gene products that, when absent, increase morphological variation. Overrepresented among these capacitors are gene products that control chromosome organization and DNA integrity, RNA elongation, protein modification, cell cycle, and response to stimuli such as stress. Capacitors have a high number of synthetic-lethal interactions but knockouts of these genes do not tend to cause severe decreases in growth rate. Each capacitor can be classified based on whether or not it is encoded by a gene with a paralog in the genome. Capacitors with a duplicate are highly connected in the protein-protein interaction network and show considerable divergence in expression from their paralogs. In contrast, capacitors encoded by singleton genes are part of highly interconnected protein clusters whose other members also tend to affect phenotypic variability or fitness. These results suggest that buffering and release of variation is a widespread phenomenon that is caused by incomplete functional redundancy at multiple levels in the genetic architecture. | 18,986,213 |
Clinical responses to gene therapy in joints of two subjects with rheumatoid arthritis. | This paper provides the first evidence of a clinical response to gene therapy in human arthritis. Two subjects with rheumatoid arthritis received ex vivo, intraarticular delivery of human interleukin-1 receptor antagonist (IL-1Ra) cDNA. To achieve this, autologous synovial fibroblasts were transduced with a retrovirus, MFG-IRAP, carrying IL-1Ra as the transgene, or remained as untransduced controls. Symptomatic metacarpophalangeal (MCP) joints were injected with control or transduced cells. Joints were clinically evaluated on the basis of pain; the circumference of MCP joint 1 was also measured. After 4 weeks, joints underwent surgical synovectomy. There were no adverse events in either subject. The first subject responded dramatically to gene transfer, with a marked and rapid reduction in pain and swelling that lasted for the entire 4 weeks of the study. Remarkably, joints receiving IL-1Ra cDNA were protected from flares that occurred during the study period. Analysis of RNA recovered after synovectomy revealed enhanced expression of IL-1Ra and reduced expression of matrix metalloproteinase-3 and IL-1beta. The second subject also responded with reduced pain and swelling. Thus, gene transfer to human, rheumatoid joints can be accomplished safely to produce clinical benefit, at least in the short term. Using this ex vivo procedure, the transgene persisted within the joint for at least 1 month. Further clinical studies are warranted. | 18,986,219 |
Vitamin D2 potentiates axon regeneration. | To date, the use of autograft tissue remains the "gold standard" technique for repairing transected peripheral nerves. However, the recovery is suboptimal, and neuroactive molecules are required. In the current study, we focused our attention on vitamin D, an FDA-approved molecule whose neuroprotective and neurotrophic actions are increasingly recognized. We assessed the therapeutic potential of ergocalciferol--the plant-derived form of vitamin D, named vitamin D2--in a rat model of peripheral nerve injury and repair. The left peroneal nerve was cut out on a length of 10 mm and immediately autografted in an inverted position. After surgery, animals were treated with ergocalciferol (100 IU/kg/day) and compared to untreated animals. Functional recovery of hindlimb was measured weekly, during 10 weeks post-surgery, using a walking track apparatus and a numerical camcorder. At the end of this period, motor and sensitive responses of the regenerated axons were calculated and histological analysis was performed. We observed that vitamin D2 significantly (i) increased axogenesis and axon diameter; (ii) improved the responses of sensory neurons to metabolites such as KCl and lactic acid; and (iii) induced a fast-to-slow fiber type transition of the Tibialis anterior muscle. In addition, functional recovery was not impaired by vitamin D supplementation. Altogether, these data indicate that vitamin D potentiates axon regeneration. Pharmacological studies with various concentrations of the two forms of vitamin D (ergocalciferol vs. cholecalciferol) are now required before recommending this molecule as a potential supplemental therapeutic approach following nerve injury. | 18,986,226 |
Voxel-based morphometry in Alzheimer's disease. | Recent morphometric MRI studies have investigated brain volume abnormalities associated with the diagnosis of Alzheimer's disease (AD) using voxel-based morphometry (VBM). This technique allows the assessment of gray matter volumes in subjects with AD or related conditions compared with healthy controls in an automated fashion, across the whole brain. This article reviews VBM findings related to different AD stages and its prodrome, mild cognitive impairment. These findings include not only gray matter deficits in medial temporal structures as seen in former MRI studies of AD conducted using manual region-of-interest measurements, but also volume changes in several other brain regions not assessed in previous MRI studies. We also discuss potential applications of VBM to improve AD diagnostic accuracy in routine clinical practice. Finally, we highlight future research directions in this field, including: investigations on the relationship between VBM findings of multifocal gray matter deficits and changes in white matter tracts that interconnect such regions; the need for population-based VBM studies using large AD samples; and the potential of studies combining VBM measurements with other potential biological markers (such as brain imaging indices of amyloid-beta deposition and cerebrospinal fluid AD markers) to further advance our knowledge about the physiopathology of AD. | 18,986,240 |
Lr34-mediated leaf rust resistance in wheat: transcript profiling reveals a high energetic demand supported by transient recruitment of multiple metabolic pathways. | The wheat gene Lr34 confers partial resistance to all races of Puccinia triticina, the causal agent of wheat leaf rust. However, the biological basis for the exceptional durability of Lr34 is unclear. We used the Affymetrix GeneChip Wheat Genome Array to compare transcriptional changes of near-isogenic lines of Thatcher wheat in a compatible interaction, an incompatible interaction conferred by the resistance gene Lr1, and the race-nonspecific response conditioned by Lr34 3 and 7 days postinoculation (dpi) with P. triticina. No differentially expressed genes were detected in Lr1 plants at either timepoint whereas, in the compatible Thatcher interaction, differentially expressed genes were detected only at 7 dpi. In contrast, differentially expressed genes were identified at both timepoints in P. triticina-inoculated Lr34 plants. At 3 dpi, upregulated genes associated with Lr34-mediated resistance encoded various defense and stress-related proteins, secondary metabolism enzymes, and transcriptional regulation and cellular-signaling proteins. Further, coordinated upregulation of key genes in several metabolic pathways that can contribute to increased carbon flux through the tricarboxylic cycle was detected. This indicates that Lr34-mediated resistance imposes a high energetic demand that leads to the induction of multiple metabolic responses to support cellular energy requirements. These metabolic responses were not sustained through 7 dpi, and may explain why Lr34 fails to inhibit the pathogen fully but does increase the latent period. | 18,986,248 |
Suppression of reactive oxygen species and enhanced stress tolerance in Rubia cordifolia cells expressing the rolC oncogene. | It is known that expression of the Agrobacterium rhizogenes rolC gene in transformed plant cells causes defense-like reactions, such as increased phytoalexin production and expression of pathogenesis-related proteins. In the present study, we examined whether this phenomenon is associated with increased production of reactive oxygen species (ROS). Single-cell assays based on confocal microscopy and fluorogenic dyes (2,7-dichlorofluorescein diacetate and dihydrorhodamine 123) showed reduced steady-state levels of ROS in rolC-expressing Rubia cordifolia cells as compared with normal cells. Paraquat, a ROS inducer, caused significant ROS elevation in normal cells but had little effect on rolC-transformed cells. Likewise, ROS elevation triggered by a light stress was suppressed in transformed cells. Our results indicate that the rolC gene acts as a ROS suppressor in unstressed cells and its expression prevents stress-induced ROS elevations. We detected a two- to threefold increase in tolerance of rolC-transformed cells to salt, heat, and cold treatments. Simultaneously, rolC-transformed cells maintained permanently active defensive status, as found by measuring isochorismate synthase gene expression and anthraquinone production. Thus, the oncogene provoked multiple effects in which ROS production and phytoalexin production were clearly dissociated. | 18,986,252 |
A common African polymorphism abolishes tyrosine sulfation of human anionic trypsinogen (PRSS2). | Human pancreatic trypsinogens undergo post-translational sulfation on Tyr(154), catalysed by the Golgi-resident enzyme tyrosylprotein sulfotransferase 2. Sequence alignments suggest that the sulfation of Tyr(154) is facilitated by a unique sequence context which is characteristically found in primate trypsinogens. In the search for genetic variants that might alter this sulfation motif, we identified a single nucleotide polymorphism (c.457G>C) in the PRSS2 (serine protease 2, human anionic trypsinogen) gene, which changed Asp(153) to a histidine residue (p.D153H). The p.D153H variant is common in subjects of African origin, with a minor allele frequency of 9.2%, whereas it is absent in subjects of European descent. We demonstrate that Asp(153) is the main determinant of tyrosine sulfation in anionic trypsinogen, as both the natural p.D153H variation and the p.D153N mutation result in a complete loss of trypsinogen sulfation. In contrast, mutation of Asp(156) and Glu(157) only slightly decrease tyrosine sulfation, whereas mutation of Gly(151) and Pro(155) has no effect. With respect to the biological relevance of the p.D153H variant, we found that tyrosine sulfation had no significant effect on the activation of anionic trypsinogen or the catalytic activity and inhibitor sensitivity of anionic trypsin. Taken together with previous studies, the observations of the present study suggest that the primary role of trypsinogen sulfation in humans is to stimulate autoactivation of PRSS1 (serine protease 1, human cationic trypsinogen), whereas the sulfation of anionic trypsinogen is unimportant for normal digestive physiology. As a result, the p.D153H polymorphism which eliminates this modification could become widespread in a healthy population. | 18,986,305 |
Clinical study of cryosurgery efficacy in the treatment of skin and subcutaneous tumors in dogs and cats. | To evaluate the efficacy of cryosurgery for treatment of skin and subcutaneous tumors in dogs and cats. Prospective study. Dogs (n=20), cats (10). Cutaneous or subcutaneous tumors were treated by liquid nitrogen cryosurgical spray (1 cm from target tissue at 90 degrees until a 5-mm halo of frozen tissue was achieved) for 15-60 seconds. Malignant lesions had 3 freeze-thaw cycles benign tumors, 2 cycles. The second or third freeze cycle was performed after complete thaw of the preceding freeze. Wounds healed by second intention. Follow-up was weekly for 1 month and then twice monthly until wounds healed, and final outcome was determined by telephone interview of owners. Tumor size ranged from 0.3 to 11 cm diameter with 28 (60%) being 0.3-1 cm; 8 (17%) 1.1-3 cm, and 11 (23%) >3.4 cm. Complications included edema, erythema and for extremity lesions, pain and lameness. Treated lesions (n=47) had an overall remission of 98% (mean follow-up, 345+/-172.02 days [range, 150-750 days]). One malignant peripheral nerve sheath tumor recurred 7 months after cryosurgical treatment. Cryosurgery is an efficient method for treatment of skin and subcutaneous tumors in dogs and cats. Cryosurgical ablation is an effective means of treating small cutaneous or subcutaneous tumors in dogs and cats, especially in older animals where wound closure or cosmetic outcome might limit surgical excision alone. | 18,986,310 |
TP53 gene mutations in canine osteosarcoma. | To investigate mutations of the TP53 gene in canine osteosarcoma (OS). Clinical historic cohort study. Client-owned dogs. OS (n=59) were screened for mutations of the complete TP53 gene using polymerase chain reaction and the mutation was analyzed by single-strand conformational polymorphism. Clinical outcome of dogs with TP53-mutated OS were compared with dogs with OS without a mutation after complete surgical excision of the primary tumor. TP53 gene mutations were observed in 24 of 59 (40.7%) OS; 3 mutated OS had 2 mutations. The alterations consisted mainly of point mutations (74%). Dogs with mutated OS had a significantly shorter survival time (ST) after surgery than dogs with normal tumor TP53 gene expression (P=.03). Other significant prognosticators for ST and disease-free interval included elevated serum alkaline phosphatase (P<.01) and tumor grade (P=.01). TP53 genetic mutations are common in canine OS and may have a prognostic value. Mutations of the TP53 gene may influence survival and should be considered when evaluating canine OS. | 18,986,312 |
Hypotonic water as adjuvant therapy for incompletely resected canine mast cell tumors: a randomized, double-blind, placebo-controlled study. | To evaluate efficacy of hypotonic water as adjuvant therapy after marginal resection of canine mast cell tumors (MCT). Double-blinded, placebo-controlled, prospective, randomized study. Dogs (n=30) with spontaneous, cutaneous, solitary MCT. The wound bed of MCT, resected with margins <0.5 cm, was injected with either hypotonic or isotonic water according to a standardized protocol. Follow-up was obtained by clinical examination at 1, 2, 3, 6, and 12 months and annual telephone contact with the owner. Eighteen dogs were treated with isotonic lactated Ringer's solution and 12 dogs with hypotonic distilled water. All MCT were stage 0 tumors and most grade II. Six tumors (4 isotonic, 2 hypotonic) recurred locally, 3 of these dogs died from disease-related reasons within 4 months. The surviving 3 dogs were alive with a median survival time (ST) of 1092 days. The calculated 2-year recurrence-free rate was 92.7%; the 2-year disease-free rate 79.1%; and the 2-year survival rate 89.5%. No significant differences in local recurrence and ST were observed between treatment groups. Histologic grading was the only significant prognosticator for ST and recurrence-free periods. No significant differences in local recurrence and ST were observed between adjunctive hypotonic water and placebo treatment after marginal resection of solitary MCT. Hypotonic water does not decrease the rate of local recurrence in dogs with solitary MCT after marginal surgical excision. | 18,986,315 |
Cardiac-specific overexpression of the human short CLC-3 chloride channel isoform in mice. | 1. ClC-3 has been proposed as a molecular candidate responsible for volume-sensitive outwardly rectifying anion channels (VSOAC) in cardiac and smooth muscle cells. To further test this hypothesis, we produced a novel line of transgenic mice with cardiac-specific overexpression of the human short ClC-3 isoform (hsClC-3). 2. Northern and western blot analyses demonstrated that mRNA and protein levels of the short isoform (sClC-3) in the heart were significantly increased in hsClC-3-overexpressing (OE) mice compared with wild-type (WT) mice. Heart weight : bodyweight ratios for OE mice were significantly smaller compared with age-matched WT mice. 3. Electrocardiogram recordings indicated no difference at rest, whereas echocardiographic recordings revealed consistent reductions in left ventricular diastolic diameter, left ventricular posterior wall thickness at end of diastole and interventricular septum thickness in diastole in OE mice. 4. The VSOAC current densities in atrial cardiomyocytes were significantly increased by ClC-3 overexpression compared with WT cells. No differences in VSOAC current properties in OE and WT atrial myocytes were observed in terms of outward rectification, anion permeability (I(-) > Cl(-) > Asp(-)) and inhibition by 4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid and glibenclamide. The VSOAC in atrial myocytes from both groups were totally abolished by phorbol-12,13-dibutyrate (a protein kinase C activator) and by intracellular dialysis of an N-terminal anti-ClC-3 antibody. 5. Cardiac cell volume measurements revealed a significant acceleration of the rate of regulatory volume decrease (RVD) in OE myocytes compared with WT. 6. In conclusion, enhanced VSOAC currents and acceleration of the time-course of RVD in atrial myocytes of OE mice is strong evidence supporting an essential role of sClC-3 in native VSOAC function in mouse atrial myocytes. | 18,986,326 |
Pityriasis rubra pilaris exacerbation with topical use of imiquimod. | The role of immune response modifiers is increasing in the treatment of dermatologic diseases. Imiquimod, a toll-like receptor agonist, results in up-regulation of proinflammatory cytokines for improved immune surveillance. Although topical use is generally well-tolerated, imiquimod can potentially result in systemic effects and exacerbate generalized inflammatory papulosquamous diseases of the skin. We report the case of a 67-year-old man who was treated with imiquimod for actinic keratosis and developed fever and a progressive erythematous papulosquamous eruption that was histologically consistent with pityriasis rubra pilaris. | 18,986,361 |
Influences of gender and age on relationships between alcohol drinking and atherosclerotic risk factors. | Alcohol drinking affects atherosclerotic progression mainly through blood pressure and lipid metabolism. The purpose of the present study was to clarify whether effects of alcohol drinking on atherosclerotic risk factors differ by gender and age. The database of periodic health check-ups for local district workers was used. The subjects were divided into 3 groups according to mean ethanol consumption per day (nondrinkers; light drinkers, less than 30 g per day; moderate-to-heavy drinkers, 30 g or more per day). The mean levels of each atherosclerosis-related variable in the 3 groups were compared. The mean level of body mass index (BMI) was slightly but significantly lower in drinkers than in nondrinkers in the thirties, forties, and fifties age groups in men and in the twenties, thirties, forties, and fifties age groups in women, while this tendency was not found in the sixties age groups of men and women. In men, mean blood pressure was higher in moderate-to-heavy drinkers than in nondrinkers in all age groups and was higher in light drinkers than in nondrinkers only in the age groups after 40 years. Mean blood pressure of women was higher in the moderate-to-heavy drinker group than in the nondrinker group and this difference became higher with advance of age. In women, mean blood pressure was not affected by light drinking in any of the age groups except for the fifties age group. In men, serum total cholesterol was higher in drinkers than in nondrinkers in the twenties age group but was lower in drinkers than in nondrinkers at thirties or older. Serum total cholesterol in women was lower in drinkers than in nondrinkers in the age groups from twenties to forties but tended to be higher in drinkers than in nondrinkers in the sixties age group. Serum HDL cholesterol increased with advance of age from thirties to sixties in men, while it decreased with advance of age from twenties to sixties in women. Serum HDL cholesterol was higher in drinkers than in nondrinkers in all age groups of men and women, and atherogenic index, calculated by using serum total cholesterol and HDL cholesterol concentrations, was lower in drinkers than in nondrinkers in all age groups of men and women. Both in men and women, blood pressure and HDL cholesterol were strongly affected by alcohol drinking: the elevating effect of alcohol drinking on blood pressure was more prominent in the elderly than in the young, while the elevating effect of alcohol drinking on serum HDL cholesterol was not influenced by age. Relationships of drinking with total cholesterol and BMI vary by age and gender. | 18,986,376 |
Prospective monitoring of BCR-ABL1 transcript levels in patients with Philadelphia chromosome-positive acute lymphoblastic leukaemia undergoing imatinib-combined chemotherapy. | The clinical significance of minimal residual disease (MRD) is uncertain in patients with Philadelphia chromosome-positive acute lymphoblastic leukaemia (Ph+ ALL) treated with imatinib-combined chemotherapy. Here we report the results of prospective MRD monitoring in 100 adult patients. Three hundred and sixty-seven follow-up bone marrow samples, collected at predefined time points during a uniform treatment protocol, were analysed for BCR-ABL1 transcripts by quantitative reverse transcription polymerase chain reaction. Ninety-seven patients (97%) achieved complete remission (CR), and the relapse-free survival (RFS) rate was 46% at 3 years. Negative MRD at the end of induction therapy was not associated with longer RFS or a lower relapse rate (P = 0.800 and P = 0.964 respectively). Twenty-nine patients showed MRD elevation during haematological CR. Of these, 10 of the 16 who had undergone allogeneic haematopoietic stem cell transplantation (HSCT) in first CR were alive without relapse at a median of 2.9 years after transplantation, whereas 12 of the 13 who had not undergone allogeneic HSCT experienced a relapse. These results demonstrate that, in Ph+ ALL patients treated with imatinib-combined chemotherapy, rapid molecular response is not associated with a favourable prognosis, and that a single observation of elevated MRD is predictive of subsequent relapse, but allogeneic HSCT can override its adverse effect. | 18,986,386 |
Role of MRI in patient selection for CRT. | Magnetic resonance imaging has great potential for aiding in the selection of patients who will respond to CRT. MRI is the only imaging tool that can simultaneously assess mechanical dyssynchrony, determine the amount and location of myocardial scar tissue, and map the location of cardiac venous anatomy-three important factors in predicting a patient's response to CRT. The goal of this manuscript is to review the MRI methods that can be used in the selection of patients for CRT. | 18,986,405 |
Noncompaction myocardium imaging with multiple echocardiographic modalities. | Noncompaction myocardium of the left ventricle (LV) is a genetically heterogeneous congenital cardiomyopathy, that has only been described during the last two decades. Echocardiography plays a pivotal role as a first line diagnostic tool of this rare abnormality. The present case describes the imaging of the noncompacted myocardium using varying echocardiographic modalities. | 18,986,417 |
Echocardiographic algorithm for cardiac resynchronization. | Cardiac resynchronization therapy (CRT) has become a proven therapeutic strategy for refractory heart failure. Large clinical trials have shown a reduction in both morbidity and mortality in patients treated with CRT. Initial patient selection has relied mainly on electrocardiographic criteria that allowed identifying only 70% of responders. Accordingly, echocardiographic criteria were developed to identify dyssynchrony in the hope of improving patient selection. Multiple echocardiographic criteria have since been proposed, with no consensus as to which parameter better predicts CRT response. Although comparison studies using the different criteria are underway, the current evaluation of dyssynchrony should probably be an integrated multiparameter approach. The objective of this article is to review the role of echocardiography in the evaluation of cardiac dyssynchrony and propose a practical algorithm in order to improve CRT patient selection. | 18,986,434 |
Human mesenchymal stem cells may be involved in keloid pathogenesis. | The pathogenesis of keloid is poorly understood. Although vigorous investigations have attempted to elucidate the mechanisms or causative factors of keloid, there are little data on why keloids are very intractable and recur easily in each patient. In an attempt to analyze the possible interaction between human mesenchymal stem cells and keloid-derived fibroblasts, the dual-chamber cell-migration assay, cell proliferation, ultrastructural morphology, and Western blot analysis were used to investigate the production of the extracellular matrices of the coculture. Cell proliferation was not significantly different between keloid-derived fibroblasts and normal dermal fibroblasts during a 4-day observation period. There was a significant cell migration of human mesenchymal stem cells when keloid-derived fibroblasts were placed in the bottom chamber, compared to when normal dermal fibroblasts were placed in the same way in 8-microm diameter pore membranes (190.6 +/- 51.45 and 32.0 +/- 6.20 cells/field, respectively, P < 0.01). With 3-microm diameter pores, the human mesenchymal stem cells migrated in the pores only when the keloid-derived fibroblasts were placed in the bottom chambers (6.4 +/- 3.84 cells/field). Monolayer coculture of human mesenchymal stem cells and keloid-derived fibroblasts demonstrated further functional differentiation, such as collagen secretion and abundant rough endoplasmic reticulum. Western blot analysis of the cells in the modified dual-chamber culture demonstrated most significantly abundant fibronectin expression when the human mesenchymal stem cells contained keloid fibroblasts. The results of this study may indicate that human mesenchymal stem cells participate and recruit in keloid pathogenesis by differentiating themselves toward keloid recalcitrant formation and progression. | 18,986,439 |
Between a whale bone and the deep blue sea: the provenance of dwarf males in whale bone-eating tubeworms. | When researchers first caught a glimpse of the lush carpet of pink tubeworms covering the scattered bones of a dead grey whale 2900 m below the surface of Monterey Bay, the excitement onboard the Western Flyer (the mother ship of the remotely operated vehicle the Tiburon) must have been electrifying. The discovery of a new genus and several species of whale bone-eating Osedax tubeworms (Annelida, Siboglinidae) a mere 6 years ago from the deep sea was itself noteworthy. But what the researchers peering into the video monitors aboard the Western Flyer could not have known at that moment was that in the gelatinous tubes of those worms clung even more peculiar forms: harems of tiny, paedomorphic males of Osedax, numbering in the hundreds at times. Whereas female tubeworms bore into the marrow of whale bones (possibly via enzymes from their endosymbiotic bacteria), the dwarf males secondarily colonize the tubes of the resident females. The number of males in a female's tube increases over time in a curvilinear fashion. Dwarf males are known from all Osedax species examined to date, yet the origin of the males was an open question. In this issue, Vrijenhoek et al. provide compelling evidence that dwarf males found in the tubes of female Osedax worms are derived from a common larval pool and are unlikely to be the sons of host females or the progeny of females in the local genetic neighbourhood. This study provides an important foundation for future work on the ecology and evolution of extreme male dwarfism in Osedax and sexual size dimorphism more generally. | 18,986,491 |
Islands in the sky: the impact of Pleistocene climate cycles on biodiversity. | Genetic studies of organisms based on coalescent modeling and paleoenvironmental data, including a new study in BMC Biology of Mexican jays in the sky islands of Arizona and northern Mexico, show that populations differentiated in multiple refugia during and after glacial cycles. | 18,986,506 |
Positive correlation between genetic diversity and fitness in a large, well-connected metapopulation. | Theory predicts that lower dispersal, and associated gene flow, leads to decreased genetic diversity in small isolated populations, which generates adverse consequences for fitness, and subsequently for demography. Here we report for the first time this effect in a well-connected natural butterfly metapopulation with high population densities at the edge of its distribution range. We demonstrate that: (1) lower genetic diversity was coupled to a sharp decrease in adult lifetime expectancy, a key component of individual fitness; (2) genetic diversity was positively correlated to the number of dispersing individuals (indicative of landscape functional connectivity) and adult population size; (3) parameters inferred from capture-recapture procedures (population size and dispersal events between patches) correlated much better with genetic diversity than estimates usually used as surrogates for population size (patch area and descriptors of habitat quality) and dispersal (structural connectivity index). Our results suggest that dispersal is a very important factor maintaining genetic diversity. Even at a very local spatial scale in a metapopulation consisting of large high-density populations interconnected by considerable dispersal rates, genetic diversity can be decreased and directly affect the fitness of individuals. From a biodiversity conservation perspective, this study clearly shows the benefits of both in-depth demographic and genetic analyses. Accordingly, to ensure the long-term survival of populations, conservation actions should not be blindly based on patch area and structural isolation. This result may be especially pertinent for species at their range margins, particularly in this era of rapid environmental change. | 18,986,515 |
Knee-clicks and visual traits indicate fighting ability in eland antelopes: multiple messages and back-up signals. | Given the costs of signalling, why do males often advertise their fighting ability to rivals using several signals rather than just one? Multiple signalling theories have developed largely in studies of sexual signals, and less is known about their applicability to intra-sexual communication. We here investigate the evolutionary basis for the intricate agonistic signalling system in eland antelopes, paying particular attention to the evolutionary phenomenon of loud knee-clicking. A principal components analysis separated seven male traits into three groups. The dominant frequency of the knee-clicking sound honestly indicated body size, a main determinant of fighting ability. In contrast, the dewlap size increased with estimated age rather than body size, suggesting that, by magnifying the silhouette of older bulls disproportionately, the dewlap acts as an indicator of age-related traits such as fighting experience. Facemask darkness, frontal hairbrush size and body greyness aligned with a third underlying variable, presumed to be androgen-related aggression. A longitudinal study provided independent support of these findings. The results show that the multiple agonistic signals in eland reflect three separate components of fighting ability: (1) body size, (2) age and (3) presumably androgen-related aggression, which is reflected in three backup signals. The study highlights how complex agonistic signalling systems can evolve through the simultaneous action of several selective forces, each of which favours multiple signals. Specifically, loud knee-clicking is discovered to be an honest signal of body size, providing an exceptional example of the potential for non-vocal acoustic communication in mammals. | 18,986,518 |
Non-invasive stroke volume assessment in patients with pulmonary arterial hypertension: left-sided data mandatory. | Cardiovascular magnetic resonance (CMR) is an emerging modality in the diagnosis and follow-up of patients with pulmonary arterial hypertension (PAH). Derivation of stroke volume (SV) from the pulmonary flow curves is considered as a standard in this respect. Our aim was to investigate the accuracy of pulmonary artery (PA) flow for measuring SV. Thirty-four PAH patients underwent both CMR and right-sided heart catheterisation. CMR-derived SV was measured by PA flow, left (LV) and right ventricular (RV) volumes, and, in a subset of nine patients also by aortic flow. These SV values were compared to the SV obtained by invasive Fick method. For SV by PA flow versus Fick, r = 0.71, mean difference was -4.2 ml with limits of agreement 26.8 and -18.3 ml. For SV by LV volumes versus Fick, r = 0.95, mean difference was -0.8 ml with limits of agreement of 8.7 and -10.4 ml. For SV by RV volumes versus Fick, r = 0.73, mean difference -0.75 ml with limits of agreement 21.8 and -23.3 ml. In the subset of nine patients, SV by aorta flow versus Fick yielded r = 0.95, while in this subset SV by pulmonary flow versus Fick yielded r = 0.76. For all regression analyses, p < 0.0001. In conclusion, SV from PA flow has limited accuracy in PAH patients. LV volumes and aorta flow are to be preferred for the measurement of SV. | 18,986,524 |
MetaFIND: a feature analysis tool for metabolomics data. | Metabolomics, or metabonomics, refers to the quantitative analysis of all metabolites present within a biological sample and is generally carried out using NMR spectroscopy or Mass Spectrometry. Such analysis produces a set of peaks, or features, indicative of the metabolic composition of the sample and may be used as a basis for sample classification. Feature selection may be employed to improve classification accuracy or aid model explanation by establishing a subset of class discriminating features. Factors such as experimental noise, choice of technique and threshold selection may adversely affect the set of selected features retrieved. Furthermore, the high dimensionality and multi-collinearity inherent within metabolomics data may exacerbate discrepancies between the set of features retrieved and those required to provide a complete explanation of metabolite signatures. Given these issues, the latter in particular, we present the MetaFIND application for 'post-feature selection' correlation analysis of metabolomics data. In our evaluation we show how MetaFIND may be used to elucidate metabolite signatures from the set of features selected by diverse techniques over two metabolomics datasets. Importantly, we also show how MetaFIND may augment standard feature selection and aid the discovery of additional significant features, including those which represent novel class discriminating metabolites. MetaFIND also supports the discovery of higher level metabolite correlations. Standard feature selection techniques may fail to capture the full set of relevant features in the case of high dimensional, multi-collinear metabolomics data. We show that the MetaFIND 'post-feature selection' analysis tool may aid metabolite signature elucidation, feature discovery and inference of metabolic correlations. | 18,986,526 |
The synchronous occurrence of squamous cell carcinoma and gastrointestinal stromal tumor (GIST) at esophageal site. | Esophageal squamous cell carcinoma is a relative common malignancy with a very poor prognosis, even adopting an integrated and multidisciplinary approach. According to the literature, gastrointestinal stromal tumors (GISTs) rarely originate from the esophagus. Moreover there are not reports of synchronous occurrence of squamous cell carcinoma and GIST at esophageal site. We describe a case of a 74 year old patient who underwent surgery for squamous cell carcinoma of the lower third of the esophagus with an incidental pathologic diagnosis of a concomitant GIST in the thoracic tract. In literature there is no evidence of concomitant squamous carcinoma and GIST of the thoracic esophagus, even if esophageal GISTs are sometimes described. The occasional finding of this neoplastic lesion underlines the importance of a carefully pathological diagnosis for its identification. Surgery, followed by a multidisciplinary approach remains the first-line treatment in both squamous and stromal neoplasm. | 18,986,537 |
Integrated weighted gene co-expression network analysis with an application to chronic fatigue syndrome. | Systems biologic approaches such as Weighted Gene Co-expression Network Analysis (WGCNA) can effectively integrate gene expression and trait data to identify pathways and candidate biomarkers. Here we show that the additional inclusion of genetic marker data allows one to characterize network relationships as causal or reactive in a chronic fatigue syndrome (CFS) data set. We combine WGCNA with genetic marker data to identify a disease-related pathway and its causal drivers, an analysis which we refer to as "Integrated WGCNA" or IWGCNA. Specifically, we present the following IWGCNA approach: 1) construct a co-expression network, 2) identify trait-related modules within the network, 3) use a trait-related genetic marker to prioritize genes within the module, 4) apply an integrated gene screening strategy to identify candidate genes and 5) carry out causality testing to verify and/or prioritize results. By applying this strategy to a CFS data set consisting of microarray, SNP and clinical trait data, we identify a module of 299 highly correlated genes that is associated with CFS severity. Our integrated gene screening strategy results in 20 candidate genes. We show that our approach yields biologically interesting genes that function in the same pathway and are causal drivers for their parent module. We use a separate data set to replicate findings and use Ingenuity Pathways Analysis software to functionally annotate the candidate gene pathways. We show how WGCNA can be combined with genetic marker data to identify disease-related pathways and the causal drivers within them. The systems genetics approach described here can easily be used to generate testable genetic hypotheses in other complex disease studies. | 18,986,552 |
Epidemiologic study on penile cancer in Brazil. | To assess epidemiologic characteristics of penile cancer in Brazil. From May 2006 to June 2007, a questionnaire was distributed to all Brazilian urologists. Their patients' clinical and epidemiological data was analyzed (age, race, place of residence, history of sexually transmitted diseases, tobacco smoking, performance of circumcision, type of hospital service), as well as the time between the appearance of the symptoms and the diagnosis, the pathological characteristics of the tumor (histological type, degree, localization and size of lesion, stage of disease), the type of treatment performed and the present state of the patient. 283 new cases of penile cancer in Brazil were recorded. The majority of these cases occurred in the north and northeast (53.02%) and southeast (45.54%) regions. The majority of patients (224, or 78.96%) were more than 46 years of age while only 21 patients (7.41%) were less than 35 years of age. Of the 283 patients presenting penile cancer, 171 (60.42%) had phimosis with the consequent impossibility to expose the glans. A prior medical history positive for HPV infection was reported in 18 of the 283 cases (6.36%). In 101 patients (35.68%) tobacco smoking was reported. The vast majority of the cases (n = 207; 73.14%) presented with tumors localized in the glans and prepuce. In 48 cases (16.96%) the tumor affected the glans, the prepuce and the corpus penis; in 28 cases (9.89%) the tumor affected the entire penis. The majority of the patients (n = 123; 75.26%) presented with T1 or T2; only 9 patients (3.18%) presented with T4 disease. Penile cancer is a very frequent pathology in Brazil, predominantly affecting low income, white, uncircumcised patients, living in the north and northeast regions of the country. | 18,986,562 |
Complications following urethral reconstructive surgery: a six year experience. | We present a single institutional experience over 6 years of intra and postoperative complications following urethral reconstructive surgery, and the impact of these complications on overall results. From June 2000 through May 2006, 153 consecutive urethral reconstructive procedures were performed on 128 patients by one surgeon (CMG). Complication rates were determined, and subgroups were categorized based on stricture etiology, patient age, length of stricture, location of stricture, type of repair, and presence of various co-morbid conditions. Overall, 23 of 153 cases (15%) had an intra or postoperative complication with a mean follow-up time of 28.3 months (range 3 to 74). The most common complications were related to infection (n = 9). Other complications included repair breakdown (n = 4), bleeding (n = 4), fistulae (n = 3), thromboembolic (n = 2), positioning-related (n = 2), and Foley catheter malfunction (n = 1). Complication rates for anastomotic and substitution urethroplasty were 9.1% (4/44) and 17% (19/109), respectively. The number of patients with at least one year of follow-up who had a complication and eventual stricture recurrence was 20% (4/20), while only 7.4% (7/95) of those who did not have a complication recurred (p = 0.08). Complications following reconstructive surgery for urethral stricture disease were mostly related to infection or repair breakdown in the immediate postoperative period. It does not appear that an intra or postoperative complication following urethral reconstructive surgery impacts the chance of eventual stricture recurrence at intermediate follow-up. | 18,986,563 |
Prevention of non-enzymic glycation of proteins by dietary agents: prospects for alleviating diabetic complications. | The accumulation of advanced glycation endproducts (AGE) due to non-enzymic glycation of proteins has been implicated in several pathophysiologies associated with ageing and diabetes. The formation of AGE is accelerated in hyperglycaemic conditions, which alter the structure and function of long-lived proteins. Thus inhibition of the formation of AGE is believed to play a role in the prevention of diabetic complications. In the present study we evaluated the antiglycating effect of aqueous extracts of various plant-based foods. The effect of aqueous extracts of these agents in terms of their ability to prevent the accumulation of AGE due to fructose-mediated in vitro glycation of eye lens soluble proteins was investigated. The degree of protein glycation in the absence and presence of dietary extracts was assessed by different complementary methods, i.e. non-tryptophan AGE fluorescence, AGE-induced cross-linking by SDS-PAGE and glyco-oxidative damage by carbonyl assay. Five out of the seventeen agents tested showed significant inhibitory potential against in vitro protein glycation in a dose-dependent manner. Prominent among them were ginger, cumin, cinnamon, black pepper and green tea, which inhibited in vitro AGE formation to lens proteins 40-90 % at 1.0 mg/ml concentration. Assessing their potential to reduce the amount of glycated protein using boronate affinity chromatography and also their ability to prevent the formation of specific antigenic-AGE structures by immunodetection further substantiated the importance of ginger, cumin and cinnamon in reducing AGE burden. These findings indicate the potential of some dietary components to prevent and/or inhibit protein glycation. Thus these dietary agents may be able to be exploited for controlling AGE-mediated diabetic pathological conditions in vivo. | 18,986,599 |
Chromatic aberrations in the field evaporation behavior of small precipitates. | Artifacts in the field evaporation behavior of small precipitates have limited the accuracy of atom probe tomography analysis of clusters and precipitates smaller than 2 nm. Here, we report on specific observations of reconstruction artifacts that were obtained in case of precipitates with radii less than 10 nm in Al alloys, focusing particularly on a shift that appears in the relative positioning of matrix and precipitate atoms. We show that this chemically dependent behavior, referred to as "chromatic aberration," is due to the electrostatic field above the emitter and the variations in field evaporation of the elements constituting the precipitates. | 18,986,609 |
[Management of premature ejaculation in adults]. | Premature ejaculation is a very frequent form of sexual dysfunction characterized by loss of control of ejaculation, inducing performance anxiety and, consequently, impaired quality of life of patients and their partners. The pathophysiology of this symptom is often both psychogenic and organic. The various organic causes must be systematically investigated. Several drug treatments are used with varying degrees of efficacy and their adverse effects must be taken into account when choosing a molecule. Psychological management is an essential complement to drug treatment. | 18,986,627 |
[Prevalence and severity of erectile dysfunction in a population with coronary insufficiency: monocentric study]. | To study prevalence and severity of erectile dysfunction (ED) in a population of men treated in emergency for a coronaropathy. The files of 200 patients who underwent a coronarography in urgency before the 1st of January 2007 were reviewed retrospectively. The following data were collated: epidemiological data and detailed breakdown of affected coronary arteries. The following patients were excluded from the current study: age over 65, past history of prostate surgery or pelvic external beam radiation therapy. The international index of erectile function (IIEF-5) questionnaire was sent by regular mail. Patients were classified according to the severity of ED: "no ED" between 21 and 25 inclusive, "mild ED" less than 21, "moderate ED" less than 17 and "strong ED" less than 10. Overall, 78 patients were included with a median age of 58 years. Prevalence of DE was 0.82 and median length of evolution was 9 months before coronary syndrome. Forty-nine patients (62.8%) had an ED classified between moderate and strong. ED was significantly associated with the group of patients smoking more than 20 cigarettes a day for at least 10 years (N = 44; P = 0.01) and with the group of patients older than 60 years (N = 38; P = 0.02). There was an association between the severity of the coronary disease and an ED classified between moderate and strong (P = 0.03). This study corroborates the existence of a strong link between ED and coronary disease, notably in patients under 65 years of age. In addition, it seems that the severity of ED is directly related with the anatomical severity of coronary disease. | 18,986,632 |
Incidence and risk factors for surgical intervention after uterine artery embolization. | To determine the incidence and risk factors for surgical intervention after uterine artery embolization for symptomatic uterine fibroids. Electronic medical records of all patients who underwent uterine artery embolization for symptomatic uterine leiomyomata were reviewed. Logistic regression was used to identify independent risk factors for any surgical intervention and for hysterectomy alone after uterine artery embolization. Uterine artery embolization was performed in 454 patients during the study period, with a median follow-up time (range) of 14 (0-128) months. Overall, 99 patients (22%) underwent any surgical intervention after uterine artery embolization in the operating room. Risk factors for any surgical intervention included younger age (P < .003), bleeding as an indication for uterine artery embolization (P < .01), presence of significant collateral ovarian vessel contribution to the uterus (P < .01), or use of 355-500 mum particles (P < .008). Patients undergoing uterine artery embolization have a 22% risk for requiring additional surgical intervention, but overall uterine artery embolization is an effective minimally invasive option. | 18,986,639 |
An E3 ubiquitin ligase, Really Interesting New Gene (RING) Finger 41, is a candidate gene for anxiety-like behavior and beta-carboline-induced seizures. | Identification of the genes underlying psychiatric illness remains a thorny problem. Previously, Quantitative Trait Loci (QTL) for anxiety-like behaviors and beta-carboline-induced seizure vulnerability have been mapped to the distal portion of mouse chromosome 10, with crosses of A/J and C57BL6 mice. An interval specific congenic strain for this chromosomal 10 region facilitated the genetic dissection of novelty-induced exploratory behaviors. By microarray studies, an unsuspected E3 ubiquitin ligase, Really Interesting New Gene (RING) Finger 41 (Rnf41) was differentially expressed in the region of interest, being upregulated in the hippocampi of B6 compared with A/J as well as congenic A.B6(chr10) versus A/J. By quantitative real-time polymerase chain reaction (qRT-PCR), Rnf41 expression levels were significantly increased 1.5- and 1.3-fold in the hippocampi of C57BL6/J and A.B6(chr10) mice compared with A/J mice, respectively. Protein levels of Rnf41 were increased in hippocampi of B6 mice compared with A/J mice across postnatal development with a 5.5-fold difference at P56. Yeast two-hybrid studies searching for Rnf41 binding partners in fetal hippocampus identified several potential targets. An interaction between Rnf41 and NogoA was validated by glutathionine-S-transferase-Rnf41 pulldown experiments. Re-analysis of a microarray database of human postmortem prefrontal cortex (Brodmann's Area 46/10) found that RNF41 messenger RNA expression levels were reduced significantly in patients with major depression and bipolar disorder compared with unaffected control subjects and confirmed by qRT-PCR. Overall, Rnf41 is nominated as a candidate gene for anxiety-like behaviors, depression, and vulnerability to seizures. The RNF41 and its binding partners suggest molecular pathways underlying behavior, highlighting a potential role for the ubiquitin proteasome system in psychiatric illness. | 18,986,647 |
Gait synchronized force modulation during the stance period of one limb achieved by an active partial body weight support system. | Our purpose was to demonstrate the ability of an actively controlled partial body weight support (PBWS) system to provide gait synchronized support during the stance period of a single lower extremity while examining the affect of such a support condition on gait asymmetry. Using an instrumented treadmill and a motion capture system, we compared gait parameters of twelve healthy elderly subjects (age 65-80 years) during unsupported walking to those while walking with 20% body weight support provided during only the stance period of the right limb. Specifically, we examined peak three-dimensional ground reaction force (GRF) data and the symmetry of lower extremity sagittal plane joint angles and of time and distance parameters. A reduction in all three GRF components was observed for the supported limb during modulated support. Reductions observed in the vertical GRF were comparable to the desired 20% support level. Additionally, GRF components examined for the unsupported limb during modulated support were consistently similar to those measured during unsupported walking. Modulated support caused statistically significant increases in asymmetry for knee flexion during stance (increased 5.9%), hip flexion during late swing (increased 9.1%), and the duration of single limb support (increased 2.8%). However, the observed increases were similar or considerably less than the natural variability in the asymmetry of these parameters during unsupported walking. The ability of the active PBWS device to provide unilateral support may offer new and possibly improved applications of PBWS rehabilitation for patients with unilateral walking deficits such as hemiparesis or orthopaedic injury. | 18,986,653 |
Dental developmental pattern of the Neanderthal child from Roc de Marsal: a high-resolution 3D analysis. | The assessment of the degree of similarity or difference between Neanderthals and modern humans in their patterns of dental development remains a controversial matter. Here we report results from the microtomographic-based (SR-microCT) high-resolution structural investigation of the maxilla and mandible of the Neanderthal child from Roc de Marsal, Dordogne, France (likely from OIS 5a). Following their virtual extraction and 3D rendering, we assessed the maturational stage of each of the 41 dental elements (20 deciduous and 21 permanent) forming its mixed dentition. By using a Bayesian approach, we calculated the probability that its deciduous and permanent mandibular sequences are found within the extant human variation as illustrated by a tomographic CT-based sub-sample of 32 children (deciduous dentition) and a panoramic radiographic- and CT-based whole sample of 343 living children (permanent dentition). Results show that neither the deciduous nor the permanent mandibular sequences displayed by Roc de Marsal are precisely found within our modern comparative files. In both sequences, the most influential factor is represented by a slight discrepancy in the Neanderthal child between the stage of mineralization of the first molar, which is proportionally advanced, and the maturational level reached by its incisors, which are proportionally delayed. Following a quantitative volumetric analysis of the deciduous teeth, we suggest that this characteristic may be related to differences between Neanderthals and modern humans in absolute dental size and relative size proportions between front and cheek teeth, as well as to structural differences in dental tissue proportions. | 18,986,680 |
Use of wireless telephones and serum S100B levels: a descriptive cross-sectional study among healthy Swedish adults aged 18-65 years. | Since the late 1970s, experimental animal studies have been carried out on the possible effects of low-intensive radiofrequency fields on the blood-brain barrier (BBB), but no epidemiological study has been published to date. Using serum S100B as a putative marker of BBB dysfunction we performed a descriptive cross-sectional study to investigate whether protein levels were higher among frequent than non-frequent users of mobile and cordless desktop phones. One thousand subjects, 500 of each sex aged 18-65 years, were randomly recruited using the population registry. Data on wireless phone use were assessed by a postal questionnaire and blood samples were analyzed for S100B. The response rate was 31.4%. The results from logistic and linear regression analyses were statistically insignificant, with one exception: the linear regression analysis of latency for UMTS use, which after stratifying on gender remained significant only for men (p = 0.01; n = 31). A low p-value (0.052) was obtained for use of cordless phone (n = 98) prior to giving the blood samples indicating a weak negative association. Total use of mobile and cordless phones over time yielded odds ratio (OR) 0.8 and 95% confidence interval (CI) 0.3-2.0 and use on the same day as giving blood yielded OR=1.1, CI=0.4-2.8. This study failed to show that long- or short-term use of wireless telephones was associated with elevated levels of serum S100B as a marker of BBB integrity. The finding regarding latency of UMTS use may be interesting but it is based on small numbers. Generally, S100B levels were low and to determine whether this association - if causal - is clinically relevant, larger studies with sufficient follow-up are needed. | 18,986,685 |
Distribution of artificial radionuclides in deep sediments of the Mediterranean Sea. | Artificial radionuclides enter the Mediterranean Sea mainly through atmospheric deposition following nuclear weapons tests and the Chernobyl accident, but also through the river discharge of nuclear facility effluents. Previous studies of artificial radionuclides impact of the Mediterranean Sea have focussed on shallow, coastal sediments. However, deep sea sediments have the potential to store and accumulate pollutants, including artificial radionuclides. Deep sea marine sediment cores were collected from Mediterranean Sea abyssal plains (depth >2000 m) and analysed for (239,240)Pu and (137)Cs to elucidate the concentrations, inventories and sources of these radionuclides in the deepest areas of the Mediterranean. The activity - depth profiles of (210)Pb, together with (14)C dating, indicate that sediment mixing redistributes the artificial radionuclides within the first 2.5 cm of the sedimentary column. The excess (210)Pb inventory was used to normalize (239,240)Pu and (137)Cs inventories for variable sediment fluxes. The (239,240)Pu/(210)Pb(xs) ratio was uniform across the entire sea, with a mean value of 1.24x10(-3), indicating homogeneous fallout of (239,240)Pu. The (137)Cs/(210)Pb(xs) ratio showed differences between the eastern (0.049) and western basins (0.030), clearly significant impact of deep sea sediments from the Chernobyl accident. The inventory ratios of (239,240)Pu/(137)Cs were 0.041 and 0.025 in the western and eastern basins respectively, greater than the fallout ratio, 0.021, showing more efficient scavenging of (239,240)Pu in the water column and major sedimentation of (137)Cs in the eastern basin. Although areas with water depths of >2000 m constitute around 40% of the entire Mediterranean basin, the sediments in these regions only contained 2.7% of the (239,240)Pu and 0.95% of the (137)Cs deposited across the Sea in 2000. These data show that the accumulation of artificial radionuclides in deep Mediterranean environments is much lower than predicted by other studies from the analysis of continental shelf sediments. | 18,986,686 |
High-dose inhaled corticosteroids versus add-on long-acting beta-agonists in asthma: an observational study. | Guidelines recommend that for patients uncontrolled on inhaled corticosteroids (ICSs), step-up options include an increase in ICS dosage or addition of a long-acting beta-agonist (LABA). Controversy persists about the best option in routine practice. To compare asthma outcomes in patients whose first step-up from ICS monotherapy was by addition of LABA (LABA cohort) or increase in ICS dosage or formulation (ICS cohort). Observational study using the General Practice Research Database, comparing outcomes in the following 12 months with regression modeling allowing for baseline cohort differences: age, sex, socioeconomic status, body mass index, comorbidity (rhinitis, heart disease), smoking status, short-acting beta-agonist (SABA) use, oral corticosteroid use, and use of asthma complicating medication. We found 46,930 patients in the ICS and 17,418 in the LABA cohort. In adjusted analysis, the odds ratio (95% CI) of successful treatment (no hospitalization, no oral corticosteroid use, average daily SABA use <1 dose/d) was lower in the ICS cohort (0.75; 0.72-0.79). The adjusted odds ratio of needing rescue SABA prescriptions was higher in the ICS cohort (1.67; 1.59-1.76). However, the adjusted odds of using any oral corticosteroids were lower (0.75; 0.71-0.78), particularly of using 3 or more courses (0.50, 0.46-0.55), and the adjusted odds of respiratory hospitalization were lower (0.69; 0.59-0.81). Although symptomatic control and rescue bronchodilator use may be improved by the addition of a LABA to ICS, there may be a lower risk of severe exacerbations and hospitalizations from ICS dose increase. | 18,986,690 |
Brief Report: Interaction between social class and risky decision-making in children with psychopathic tendencies. | Adult psychopaths are thought to have risky decision-making and behavioral disinhibition, but little is known about the moderating effects of psychosocial factors and whether these associations can be observed in children with psychopathic tendencies. This study tests the biosocial hypothesis that social class will moderate psychopathy-neurocognition relationships, with these effects being stronger in children from high social classes. Preadolescent community twins (N=298) were assessed on decision-making (Iowa Gambling) and behavior inhibition (Porteus Maze) tasks, while psychopathic tendencies and socioeconomic status were assessed by the child's caregiver. A significant interaction was observed whereby risky decision-making was associated with psychopathic tendencies only in children from benign home environments. Findings support a biosocial interaction perspective on child psychopathy, suggesting that risky decision-making may particularly predispose to psychopathic traits in children from benign home backgrounds. | 18,986,696 |
Development of hepatic failure despite use of intravenous acetylcysteine after a massive ingestion of acetaminophen and diphenhydramine. | Acetylcysteine is an antidote used to prevent liver failure after acetaminophen overdose. We report the development of liver failure despite administration of intravenous acetylcysteine in a patient with massive ingestion of an acetaminophen and diphenhydramine combination product. An atypical, delayed, bimodal peak in the serum acetaminophen concentration was observed. This case suggests that individualized dosing of antidotal therapy may be needed for preparations of acetaminophen that result in delayed absorption or after massive overdose. | 18,986,731 |
Synthesis and pharmacological evaluation of a novel series of 5-(substituted)aryl-3-(3-coumarinyl)-1-phenyl-2-pyrazolines as novel anti-inflammatory and analgesic agents. | A novel series of 5-(substituted)aryl-3-(3-coumarinyl)-1-phenyl-2-pyrazolines (3a-l) were synthesized by reacting various substituted 3-aryl-1-(3-coumarinyl)propan-1-ones (2a-l) with phenylhydrazine in the presence of hot pyridine. Structures of all new synthesized compounds were characterized on the basis of elemental analysis and spectral data (IR, (1)H NMR and (13)C NMR). The title compounds were screened for in vivo anti-inflammatory and analgesic activities at a dose of 200 mg/kg b.w. Among the 12 prepared compounds, Compounds 3d, e, i and j exhibited significant anti-inflammatory activity in model of acute inflammation such as carrageenan-induced rat edema paw while compounds 3d and e showed considerable activity in model of chronic inflammation such as adjuvant-induced arthritis and were compared with diclofenac (13.5 mg/kg b.w.) as a standard drug. These compounds were also found to have significant analgesic activity in the acetic acid induced writhing model and antipyretic activity in yeast-induced pyrexia model along with minimum ulcerogenic index. | 18,986,738 |
Kinematic analyses during stair descent in young women with patellofemoral pain. | Compensatory movement strategies may develop in response to pain to avoid stress on the affected area. Patellofemoral pain is characterised by intermittent periods of pain and the present study addresses whether long-term pain leads to compensatory movement strategies that remain even when the pain is absent. Lower extremity kinematics in three dimensions was studied in stair descent in 17 women with patellofemoral and in 17 matched controls. A two-dimensional geometric model was constructed to normalise kinematic data for subjects with varying anthropometrics when negotiating stairs of fixed proportions. There were minor differences in movement patterns between groups. Knee joint angular velocity in the stance leg at foot contact was lower and the movement trajectory tended to be jerkier in the patellofemoral group. The two-dimensional model showed greater plantar flexion in the swing leg in preparation for foot placement in the patellofemoral group. The results indicate that an altered stair descent strategy in the patellofemoral group may remain also in the absence of pain. The biomechanical interpretation presumes that the strategy is aimed to reduce knee joint loading by less knee joint moment and lower impact force. | 18,986,741 |
Determination of ranolazine in human plasma by LC-MS/MS and its application in bioequivalence study. | A simple, sensitive and specific liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for quantification of ranolazine in human plasma. The analytical method consists in the precipitation of plasma sample with methanol, followed by the determination of ranolazine by an LC-MS/MS. The analyte was separated on a Peerless Cyano column (33 mm x 4.6 mm, 3 microm) an isocratic mobile phase of methanol-water containing formic acid (1.0%, v/v) (65:35, v/v) at a flow rate of 1.0 ml/min. Protonated ions formed by a turbo ionspray in positive mode were used to detect analyte and internal standard (IS). The MS/MS detection was made by monitoring the fragmentation of m/z 428.20-->279.50 for ranolazine and m/z 448.30-->285.20 for internal standard on a triple quadrupole mass spectrometer. The method was validated over the concentration range of 5-2000 ng/ml for ranolazine in human plasma with correlation coefficient of 0.9937 (S.D.: +/-0.00367, range: 0.9895-0.9963). The accuracy and precision values obtained from six different sets of quality control samples analyzed in separate occasions ranged from 94.53 to 117.86 and 0.14% to 4.56%, respectively. Mean extraction recovery was 82.36-94.25% for three quality control (QC) samples and 88.37% for IS. Plasma samples were stable for three freeze-thaw cycles, or 24h ambient storage, or 1 and 3 months storage at -20 degrees C. Processed samples (ready for injection) were stable up to 72 h at autosampler (4 degrees C). The developed method was successfully applied for analyzing ranolazine in plasma samples for a bioequivalence study with 12 healthy volunteers. | 18,986,788 |
Understanding the interpersonal impact of trauma: contributions of PTSD and depression. | To build on the growing literature on interpersonal relationships among individuals with PTSD, this study examined the separate influences of PTSD symptoms and depression on functioning with friends, romantic partners, and family. To examine the influence of measurement, both interviewer-rated assessment of interpersonal functioning and self-reported assessment of perceived social support were included. The sample included 109 community members who sought help for mental health problems in the aftermath of a serious motor vehicle accident. Building on previous research, hierarchical regression models were used to examine the impact of re-experiencing, avoidance, emotional numbing, and hyperarousal on relationship functioning, followed by depression. Results suggest that assessment modality makes a difference in understanding factors contributing to interpersonal strain. When assessed by an interviewer, depression seems to play a larger role in interpersonal strain, relative to PTSD symptoms. When assessed via self-reported perceived social support, weaker associations were observed, which highlighted the role of emotional numbing. Results are discussed in light of the possible role that PTSD comorbidity with depression plays in interpersonal functioning following a traumatic event, with implications for future research. | 18,986,792 |
Role of oxidative and nitrosative stress in cisplatin-induced nephrotoxicity. | cis-Diamminedichloroplatinum (II) (cisplatin) is an important chemotherapeutic agent useful in the treatment of several cancers; however, it has several side effects such as nephrotoxicity. The role of the oxidative and nitrosative stress in cisplatin-induced nephrotoxicity is additionally supported by the protective effect of several free radical scavengers and antioxidants. Furthermore, in in vitro experiments, antioxidants or reactive oxygen species (ROS) scavengers have a cytoprotective effect on cells exposed to cisplatin. Recently, the participation of nitrosative stress has been more explored in cisplatin-induced renal damage. The use of a water-soluble Fe(III) porphyrin complex able to metabolize peroxynitrite (ONOO(-)) has demonstrated that this anion contributes to both in vivo and in vitro cisplatin-induced toxicity. ONOO(-) is produced when nitric oxide (NO*) reacts with superoxide anion (O(2)(*-)); currently, there are evidences suggesting alterations in NO* production after cisplatin treatment and the evidence appear to NO* has a toxic effect. This article goes through current evidence of the mechanism by more than a few compounds have beneficial effects on cisplatin-induced nephrotoxicity, contribute to understanding the role of oxidative and nitrosative stress and suggest several points as part of the mechanism of cisplatin toxicity. | 18,986,801 |
Ambiguous and forbidden parameter combinations for aqueous plutonium. | The concepts of forbidden and ambiguous oxidation-state distributions for plutonium are easier to understand when presented graphically. This note describes two diagrams that illustrate the phenomena. | 18,986,812 |
On the origin of sensory impairment and altered pain perception in Prader-Willi syndrome: a neurophysiological study. | High pain threshold is a supportive diagnosis criterion for Prader-Willi syndrome (PWS), but its pathogenesis is poorly understood. In this study we investigate sensory pathways in PWS, in order to evaluate peripheral or central involvement in altered sensory perception. 14 adult PWS patients, 10 obese non-diabetic people and 10 age-matched controls underwent: (a) motor/sensory nerve conduction velocities at the upper and lower limbs; (b) palmar/plantar sympathetic skin response; (c) somatosensory evoked potentials from upper/lower limbs; (d) quantitative sensory testing to measure sensory threshold for vibration, warm and cold sensation, heat and cold-induced pain and (e) blood sample analysis to evaluate glucose and insulin levels and to calculate the quantitative insulin-sensitivity check index (QUICKI). Electroneurographic examination, sympathetic skin response and somatosensory evoked potentials were all within normal ranges. In the PWS group, thermal and pain thresholds but not vibratory were significantly higher than in healthy and obese people (p<0.05). Sensory threshold did not correlate with BMI nor with QUICKI. Our data suggest that altered perception in PWS does not seem attributable to a peripheral nerve derangement due to metabolic factors or obesity. Impairment of the small nociceptive neurons of dorsal root ganglia or involvement of hypothalamic region may not be excluded. | 18,986,815 |
The epidemiology of Crimean-Congo hemorrhagic fever in Turkey, 2002-2007. | Crimean-Congo hemorrhagic fever (CCHF) is a serious disease caused by the CCHF virus of the Bunyaviridae family. The disease has been reported in 30 countries in Africa, Asia, Eastern Europe, and the Middle East. It has been present in Turkey since 2002. In this study we present and discuss the epidemiological features, clinical and laboratory findings, treatment, and outcome of cases diagnosed with CCHF between 2002 and 2007 from the surveillance results of the Turkish Ministry of Health (MoH). According to the surveillance system of the MoH, data for patients with clinical, laboratory, and epidemiological findings compatible with CCHF are recorded on case reporting forms. These forms are submitted to the General Directorate of Primary Health Care of the MoH by the city health directorates. All the surveillance data regarding CCHF were recorded on a database (SSPS 11.0) established in the Communicable Diseases Department of the MoH. According to the surveillance reports of the Turkish MoH, between 2002 and 2007, 1820 CCHF cases occurred (150 in 2002-2003, 249 in 2004, 266 in 2005, 438 in 2006, and 717 in 2007). The crude fatality rate was calculated to be 5% (92/1820). Two thirds of the CCHF cases were reported from five cities located in the Mid-Eastern Anatolia region; 69.4% of the cases were from rural areas. The male to female ratio was 1.13:1. Of all the reported cases, 68.9% had a history of tick-bite or tick contact and 84.1% were seen in the months of May, June, and July. Of 1820 CCHF cases, three (0.16%) were nosocomial infections. CCHF appears to be a seasonal problem in the Mid-Eastern Anatolia region of Turkey. The possible risk factors for transmission and the clinical and laboratory findings of patients with a diagnosis of CCHF were found to be similar to those reported in the literature. The mean fatality rate for Turkey is lower than the rate reported for other series from other parts of the world. | 18,986,819 |
Isolated tricuspid valve endocarditis. | We present two non-HIV-infected patients with isolated native non-rheumatic tricuspid valve endocarditis who were not intravenous drug abusers. The patients presented with fever and chills. Plain radiography or high-resolution computed tomography of the chest revealed consolidation or infiltrate of the left parenchyma in both patients. Large vegetation located on the tricuspid leaflets was detected by transesophageal echocardiography. Staphylococcus aureus grew in two out of three blood cultures for one patient. Tricuspid valve endocarditis imitates illnesses with fever and pulmonary symptoms or signs of acute or chronic onset, and might be present even without abnormal chest X-rays or intravenous drug addiction. | 18,986,821 |
The plant B3 superfamily. | The plant-specific B3 superfamily encompasses well-characterized families, such as the auxin response factor (ARF) family and the LAV family, as well as less well understood families, such as RAV and REM. In Arabidopsis, there are 118 B3 genes, and in rice there are 91 B3 genes. The B3 domain is present in genes from gymnosperms, mosses and green algae, indicating that the B3 domain evolved on the plant lineage before multicellularity. The aim of this review is to phylogenetically characterize the members of the B3 family in Arabidopsis and rice and to review the function of the B3 genes that have been studied to date. | 18,986,826 |
Betapapillomaviruses: innocent bystanders or causes of skin cancer. | Human papillomaviruses (HPV) are found in almost all squamous epithelia where they can cause hyperproliferative disease of mucosa and skin. Mucosal HPV types, such as HPV6 and HPV16, are known to cause anogenital warts and dysplasia or neoplasia, respectively. These HPV types have been studied extensively, and for some of them recently preventive vaccines have become available. Although HPV that populate the skin were the first identified HPV types, knowledge of the pathogenicity of HPV in the cornified epithelia stayed behind. What the majority of cutaneous HPV types do, for instance those belonging to the beta genus (betaPV), is largely unknown. As the number of reports that describe epidemiological associations between markers of betaPV infection and skin cancer gradually increases, the need for basic knowledge about these viruses grows as well. This review aims to picture what is currently known about betaPV with respect to infection, transmission and transformation, in order to envisage their potential role in cutaneous carcinogenesis. | 18,986,829 |
Brainstem sites controlling the lower esophageal sphincter and crural diaphragm in the ferret: a neuroanatomical study. | The lower esophageal sphincter (LES) and the crural diaphragm (CD) surrounding the esophagogastric junction are key components of the gastroesophageal reflex mechanism, which engages the vago-vagal brainstem circuitry. Although both components work in conjunction to prevent gastroesophageal reflux, little is known about the brain area(s) where this integration takes place. The aims of this study were to: (1) trace the brainstem circuitry associated with the CD and the LES, and (2) determine possible sites of convergence. Experiments were done in adult male ferrets. Under isoflurane anesthesia, recombinant strains of the transneuronal pseudorabies virus (PRV-151 or PRV-Bablu) or the monosynaptic retrograde tracer cholera toxin beta-subunit (CTb) were injected into either the CD or the LES. Following a survival period of 5-7 days, animals were euthanized, perfused and their brains removed for dual-labeling immunofluorescence processing. In animals injected with recombinants of PRV into the CD and the LES, distinct labeling was found in various brainstem nuclei including: area postrema, DMV, nucleus tractus solitarius (NTS), medial reticular formation (MRF) and nucleus ambiguous (NA). Double-labeled cells were only evident in the DMV, NTS and MRF. Injections of CTb into the CD or the LES resulted in retrograde labeling only in the DMV. These findings demonstrate the presence of a direct projection from the DMV to the CD. They further suggest that the neuronal connections responsible for CD or LES function are contained in circuitries that, though largely independent, may converge at the level of DMV, NTS and MRF. | 18,986,853 |
Two-dimensional blind Bayesian deconvolution of medical ultrasound images. | A new approach to 2-D blind deconvolution of ultrasonic images in a Bayesian framework is presented. The radio-frequency image data are modeled as a convolution of the point-spread function and the tissue function, with additive white noise. The deconvolution algorithm is derived from statistical assumptions about the tissue function, the point-spread function, and the noise. It is solved as an iterative optimization problem. In each iteration, additional constraints are applied as a projection operator to further stabilize the process. The proposed method is an extension of the homomorphic deconvolution, which is used here only to compute the initial estimate of the point-spread function. Homomorphic deconvolution is based on the assumption that the point-spread function and the tissue function lie in different bands of the cepstrum domain, which is not completely true. This limiting constraint is relaxed in the subsequent iterative deconvolution. The deconvolution is applied globally to the complete radiofrequency image data. Thus, only the global part of the point-spread function is considered. This approach, together with the need for only a few iterations, makes the deconvolution potentially useful for real-time applications. Tests on phantom and clinical images have shown that the deconvolution gives stable results of clearly higher spatial resolution and better defined tissue structures than in the input images and than the results of the homomorphic deconvolution alone. | 18,986,863 |
Viscosity measurement of Newtonian liquids using the complex reflection coefficient. | This work presents the implementation of the ultrasonic shear reflectance method for viscosity measurement of Newtonian liquids using wave mode conversion from longitudinal to shear waves and vice versa. The method is based on the measurement of the complex reflection coefficient (magnitude and phase) at a solid-liquid interface. The implemented measurement cell is composed of an ultrasonic transducer, a water buffer, an aluminum prism, a PMMA buffer rod, and a sample chamber. Viscosity measurements were made in the range from 1 to 3.5 MHz for olive oil and for automotive oils (SAE 40, 90, and 250) at 15 and 22.5 degrees C, respectively. Moreover, olive oil and corn oil measurements were conducted in the range from 15 to 30 degrees C at 3.5 and 2.25 MHz, respectively. The ultrasonic measurements, in the case of the less viscous liquids, agree with the results provided by a rotational viscometer, showing Newtonian behavior. In the case of the more viscous liquids, a significant difference was obtained, showing a clear non-Newtonian behavior that cannot be described by the Kelvin-Voigt model. | 18,986,872 |
Preparation of barium titanate nanoparticle sphere arrays and their dielectric properties. | Barium titanate (BaTiO(3)) nanoparticles from 27 to 192 nm were prepared by the 2-step thermal decomposition method from barium titanyl oxalate nanoparticles. These particles were dispersed well into 1-propanol, and dense BaTiO(3); nanoparticle sphere arrays without stress-field were prepared by the meniscus method. Temperature dependence of dielectric properties was successfully measured using these dense nanoparticle sphere arrays, and size effect on dielectric properties was discussed. | 18,986,885 |
Reduction of influence of variation in center frequencies of RF echoes on estimation of artery-wall strain. | Atherosclerotic change of the arterial wall leads to a significant change in its elasticity. For assessment of elasticity, measurement of arterial wall deformation is required. For motion estimation, correlation techniques are widely used, and we have developed a phase-sensitive correlation method, namely, the phased-tracking method, to measure the regional strain of the arterial wall due to the heartbeat. Although phase-sensitive methods using demodulated complex signals require less computation in comparison with methods using the correlation between RF signals or iterative methods, the displacement estimated by such phase-sensitive methods are biased when the center frequency of the RF echo apparently varies. One of the reasons for the apparent change in the center frequency would be the interference of echoes from scatterers within the wall. In the present study, a method was introduced to reduce the influence of variation in the center frequencies of RF echoes on the estimation of the artery-wall strain when using the phase-sensitive correlation technique. The improvement in the strain estimation by the proposed method was validated using a phantom. The error from the theoretical strain profile and the standard deviation in strain estimated by the proposed method were 12.0% and 14.1%, respectively, significantly smaller than those (23.7% and 46.2%) obtained by the conventional phase-sensitive correlation method. Furthermore, in the preliminary in vitro experimental results, the strain distribution of the arterial wall well corresponded with pathology, i.e., the region with calcified tissue showed very small strain, and the region almost homogeneously composed of smooth muscle and collagen showed relatively larger strain and clear strain decay with respect to the radial distance from the lumen. | 18,986,889 |
Friction drive of an SAW Motor. Part I: measurements. | The surface acoustic wave motor in this study utilized transparent lithium niobate for a stator. We then measured the normal and tangential displacements of the frictional surface of the slider via the transparent stator by means of 2 laser Doppler vibrometers. We thoroughly inspected the measurement conditions and indicated that the measured data were reliable and usable for subsequent precise analyses of the friction drive. The driving conditions for the measurements were a driving frequency of 9.61 MHz and a wave vibration amplitude of 20 nm. The start-up transients of the motor for a duration of 10.4 micros were measured. The measurements showed that the frictional surface of the slider displaced in both the normal and tangential directions followed each wave vibration. The displacements increased with the wave's vibration amplitude: they increased to 10 nm in both directions, in response to the transient increase of the wave's vibration amplitude to 20 nm, under the 15 N preload condition. Moreover, the slider surface rotated in the same direction as the wave surface and its trajectories were a tilted elliptical orbit. Since the surface of the wave rotated in an upright elliptical orbit, the result indicated that the tangential displacement of the slider surface was delayed in relation to that of the wave. The delay was in the range from 30 degrees to 60 degrees under the 15 N preload condition. | 18,986,896 |
Equivalent circuit for broadband underwater transducers. | A method is presented to determine the equivalent circuits of broadband transducers with 2 resonances in the frequency band of interest. The circuit parameters are refined by least-squares fitting the measured electrical conductance data with this model. The method is illustrated by computing the conductance and susceptance of the equivalent circuits of 3 types of broadband transducers and comparing them with the measured values. The equivalent circuit of a transducer is necessary for designing filters that match the impedances of the transducer and the power amplifier that drives the transducer. | 18,986,904 |
Lead-free piezoelectric-metal-cavity (PMC) actuators. | A piezoelectric piezoelectric-metal-cavity (PMC) actuator was reported previously that can exhibit a large flexural displacement. In this paper, a lead-free piezoelectric ceramic was used as a driving element of the PMC actuator. Bi(0.5)(Na(0.725)K(0.175)Li(0.1))(0.5)TiO3 (abbreviated as BNKLT) is a soft-type piezoelectric ceramic with good piezoelectric properties at room temperature. Both the electrical and mechanical properties of the BNKLT PMC actuator were measured. With good piezoelectric coefficients and low density, the BNKLT ceramic has the potential to be used as the driving element of the lead-free actuator. | 18,986,912 |
Adaptive clutter filtering based on sparse component analysis in ultrasound color flow imaging. | An adaptive method based on the sparse component analysis is proposed for stronger clutter filtering in ultrasound color flow imaging (CFI). In the present method, the focal underdetermined system solver (FOCUSS) algorithm is employed, and the iteration of the algorithm is based on weighted norm minimization of the dependent variable with the weights being a function of the preceding iterative solutions. By finding the localized energy solution vector representing strong clutter components, the FOCUSS algorithm first extracts the clutter from the original signal. However, the different initialization of the basis function matrix has an impact on the filtering performance of FOCUSS algorithms. Thus, 2 FOCUSS clutter- filtering methods, the original and the modified, are obtained by initializing the basis function matrix using a predetermined set of monotone sinusoids and using the discrete Karhunen-Loeve transform (DKLT) and spatial averaging, respectively. Validation of 2 FOCUSS filtering methods has been performed through experimental tests, in which they were compared with several conventional clutter filters using simplistic simulated and gathered clinical data. The results demonstrate that 2 FOCUSS filtering methods can follow signal varying adaptively and perform clutter filtering effectively. Moreover, the modified method may obtain the further improved filtering performance and retain more blood flow information in regions close to vessel walls. | 18,986,949 |
Use of auditory learning to manage listening problems in children. | This paper reviews recent studies that have used adaptive auditory training to address communication problems experienced by some children in their everyday life. It considers the auditory contribution to developmental listening and language problems and the underlying principles of auditory learning that may drive further refinement of auditory learning applications. Following strong claims that language and listening skills in children could be improved by auditory learning, researchers have debated what aspect of training contributed to the improvement and even whether the claimed improvements reflect primarily a retest effect on the skill measures. Key to understanding this research have been more circumscribed studies of the transfer of learning and the use of multiple control groups to examine auditory and non-auditory contributions to the learning. Significant auditory learning can occur during relatively brief periods of training. As children mature, their ability to train improves, but the relation between the duration of training, amount of learning and benefit remains unclear. Individual differences in initial performance and amount of subsequent learning advocate tailoring training to individual learners. The mechanisms of learning remain obscure, especially in children, but it appears that the development of cognitive skills is of at least equal importance to the refinement of sensory processing. Promotion of retention and transfer of learning are major goals for further research. | 18,986,969 |
A 2000 km genetic wake yields evidence for northern glacial refugia and hybrid zone movement in a pair of songbirds. | Hybrid zones are natural experiments that expose the forces maintaining species differences. But for cases where a trait of one of the hybridizing pair appears shifted into the range of the other, the underlying mechanism can be difficult to infer. For example, hybridization between hermit warbler (Dendroica occidentalis) and Townsend's warbler (Dendroica townsendi) is restricted to narrow hybrid zones in Washington and Oregon, yet hermit mtDNA can be found in phenotypically pure Townsend's populations up to 2000 km north along the Pacific coast. This could reflect introgression of selectively favoured hermit mitochondria north across the hybrid zones, or a neutral genetic wake left behind following southern zone movement. Hermit mitochondrial haplotypes in populations of coastal Townsend's exhibit relatively high genetic diversity and significant divergence from those found in populations of hermit warblers. This contradicts the predictions of selective introgression, but is consistent with a northern population of hermits diverging in a glacial refugium before being replaced by Townsend's via aggressive hybridization. Previous field studies showing Townsend's males to be competitively superior to hermit males support this scenario, and suggest that the extreme hybrid zone movement evidenced by the hermit mitochondrial wake represents an extinction in progress. | 18,986,973 |
Properties of pseudo-complementary DNA substituted with weakly pairing analogs of guanine or cytosine. | A straightforward enzymatic protocol for converting regular DNA into pseudo-complementary DNA could improve the performance of oligonucleotide microarrays by generating readily hybridizable structure-free targets. Here we screened several highly destabilizing analogs of G and C for one that could be used with 2-aminoadenine (nA) and 2-thiothymine (sT) to generate structure-free DNA that is fully accessible to complementary probes. The analogs, which included bioactive bases such as 6-thioguanine (sG), 5-nitrocytosine (NitroC), 2-pyrimidinone (P; the free base of zebularine) and 6-methylfuranopyrimidinone (MefP), were prepared as dNTPs and evaluated as substrates for T7 and Phi29 DNA polymerases that lacked editor function. Pairing properties of the analogs were characterized by solution hybridization assays using modified oligonucleotides or primer extension products. P and MeP did not support robust primer extension whereas sG and NitroC did. In hybridization assays, however, sG lacked discrimination and NitroC paired too strongly to C. The dNTPs of two other base analogs, 7-nitro-7-deazahypoxanthine (NitrocH) and 2-thiocytosine (sC), exhibited the greatest promise. Either analog could be used with nA and sT to generate DNA that was nearly structure-free. Hybridization of probes to these modified DNAs will require the development of base analogs that pair strongly to NitrocH or sC. | 18,987,000 |
How frugal is Mother Nature with haplotypes? | Inference of haplotypes from genotype data is crucial and challenging for many vitally important studies. The first, and most critical step, is the ascertainment of a biologically sound model to be optimized. Many models that have been proposed rely partially or entirely on reducing the number of unique haplotypes in the solution. This article examines the parsimony of haplotypes using known haplotypes as well as genotypes from the HapMap project. Our study reveals that there are relatively few unique haplotypes, but not always the least possible, for the datasets with known solutions. Furthermore, we show that there are frequently very large numbers of parsimonious solutions, and the number increases exponentially with increasing cardinality. Moreover, these solutions are quite varied, most of which are not consistent with the true solutions. These results quantify the limitations of the Pure Parsimony model and demonstrate the imperative need to consider additional properties for haplotype inference models. At a higher level, and with broad applicability, this article illustrates the power of combinatorial methods to tease out imperfections in a given biological model. | 18,987,010 |
Response of bone subjected to optimized high dose irradiation. | Allograft tissues are used in over one million musculoskeletal procedures per year. Consequently, it is crucial tissue banks use procedures to militate against allograft associated bacterial and viral infections. Recent studies have identified an important pathogen inactivation technology for musculoskeletal allografts that utilizes high-dose gamma irradiation (50 kGy) under controlled conditions. A total dose of 50 kGy assures that the current standard for medical devices for a microbial sterility assurance level of 10(- 6) is met. Furthermore, the pathogen inactivation technology results in a greater than four log inactivation of enveloped and nonenveloped viruses. Efficacious clinical outcome from musculoskeletal allografts exposed to this innovative sterilization procedure will require that there is no performance decrement in the allograft's biological properties. Therefore, to validate this objective, we executed a study focusing on remodeling and osteoconduction of bone allografts treated with a high dose of gamma irradiation (50 kGy), radioprotectants and well-defined operating parameters of temperature and water content. A rabbit calvarial model was used to test the hypothesis that remodeling and osteoconduction of allogeneic bone treated with the new pathogen inactivation technology would be equivalent to nontreated allogeneic bone. Results indicated treated bone allografts were comparable to nontreated allografts. We conclude, therefore, that based on this outcome and other reports, that high doses of gamma irradiation under optimized conditions designed to reduce free radical damage to tissue will provide safer allografts. | 18,987,016 |
Effect of cryoprotectant incubation time on handling properties of allogeneic tendons prepared for knee ligament reconstruction. | Soft tissue tendon allografts prepared for anterior cruciate ligament reconstruction are becoming increasingly popular; although concerns exist regarding increased long-term laxity and traumatic rupture rates. This qualitative study evaluated the tissue handling properties of human tibialis posterior tendons prepared using a patented process to improve allograft remodeling and ligamentization under differing cryoprotectant incubation times over 60-min rehydration. Tendons that had been incubated for 8 h had smaller diameters than those that were incubated for 2 h (8.5 +/- 1.5 mm vs. 9.1 +/- 1.3 mm, p = 0.02). Qualitative tissue handling property results indicated that the 8-h incubation had a negative affect on tissue color. Both incubation time and rehydration time influenced tensile stiffness, compressive resilience, and ease of tissue handling for allograft preparation with the 8-h group displaying poorer results. This study concludes that an 8-h cryoprotectant incubation time is detrimental to qualitative allogeniec tibialis posterior tendon properties. Both groups tended to improve with longer rehydration times, however the 8-h incubation group remained actively dehydrated as evidenced by its smaller diameter and poorer tissue handling properties. Suboptimally rehydrated tendons would be more likely to accrue damage during allograft preparation or during implantation. | 18,987,017 |
Evaluation of parenteral depot insulin formulation using PLGA and PLA microparticles. | PLGA and PLA microparticles entrapping insulin are prepared by solvent evaporation method and are evaluated in diabetes-induced rat for its efficacy in maintaining blood sugar level from a single intramuscular dose. In vitro release of insulin from PLGA and PLA microparticles are 75.35 +/- 1.73% and 67.536 +/- 2.23%, respectively in 168 h (7 days). Released insulin from polymer particles are mostly in monomeric form without aggregation. Optimal use of stabilizers during particle formulation helps in reducing protein denaturation and thus results in stabilized insulin-loaded polymer particles. Intramuscular administration of insulin-loaded PLGA (50 : 50) and PLA microparticles (equivalent to 25 IU insulin/kg of animal weight) in alloxaninduced diabetic rats result in 53.86 +/- 4.2% and 39.52 +/- 6.7% reduction in blood glucose level, respectively in 96 h. This effect continued up to 7 days in case of PLGA and PLA microparticles. | 18,987,018 |
Enhanced regeneration of critical bone defects using a biodegradable gelatin sponge and beta-tricalcium phosphate with bone morphogenetic protein-2. | We examine the osteogenicity of a sponge biomaterial consisting of a biodegradable mixture of gelatin and beta-tricalcium phosphate (betaTCP) that bound bone morphogenetic protein 2 (BMP-2) in critical-sized bone defects in rats. Gelatin-betaTCP sponges containing either phosphate buffered saline or incorporating BMP-2 are implanted into 5 mm diameter bone defects created in rat mandibles. We assess the defects biweekly for 8 weeks following implantation. There is significantly higher osteoinductive activity and significantly more Gla-osteocalcin content at bone-defect healing sites treated with gelatin-betaTCP sponges incorporating BMP-2 than there is in those treated with sponges that did not contain BMP-2. Histologically, new bone that contains bone marrow and that is connected to the original bone almost entirely replaces the regenerated bone. These results show that biodegradable gelatin-betaTCP incorporating BMP-2 is osteogenic enough to promote healing in large bone defects. | 18,987,021 |
Effects of nitric oxide synthase inhibition on dexmedetomidine-induced vasoconstriction in healthy human volunteers. | This study aimed to assess the contribution of endothelial nitric oxide synthesis to the net responses of human peripheral blood vessels in vivo to the selective alpha(2)-adrenoceptor agonist dexmedetomidine. Two groups of healthy young men were studied. In the first experiment, after brachial plexus block, the responses of digital arteries to systemically administered dexmedetomidine (target plasma concentration 1.2 ng ml(-1)) were studied using a photoplethysmograph (n=10) during i.a. infusions of saline and the nitric oxide synthase (NOS) inhibitor N(G)-monomethyl-L-arginine (L-NMMA) (8 micromol min(-1)). In a separate experiment, after pre-treatment with acetylsalicylic acid, responses to increasing doses of dexmedetomidine (0.01-164 ng min(-1)) in the presence and absence of L-NMMA were compared in dorsal hand veins (DHV) (n=10) using linear variable differential transformers. L-NMMA significantly augmented dexmedetomidine-induced vasoconstriction of digital arteries as assessed by an increase in light transmission through a finger and by a decrease in finger temperature. The mean (95% confidence interval) extent of the additional effect of L-NMMA over the constrictor effect of dexmedetomidine alone was 19% (14-24) (P<0.0001). In DHV, L-NMMA had variable effects on the dexmedetomidine-constriction dose-response curve. In three subjects, the curve was shifted significantly to the left (with a >10-fold difference in ED(50)), but ED(50) was only marginally affected by L-NMMA in the other subjects (difference in ED(50) <five-fold). The endothelial NOS enzyme has a significant role in opposing the vasoconstrictor action of dexmedetomidine at drug concentrations within the therapeutic range. | 18,987,056 |
The use of radiotelemetry to assess the time needed to acclimatize guineapigs following several hours of ground transport. | The objective of this study was to investigate the effect of ground transportation on guineapigs. Physiological parameters, i.e. heart rate (HR), body temperature (BT) and activity (ACT), were measured before and after transport, using previously implanted radiotelemetry transmitters. Body weight was measured before and after transport. After a postsurgical recovery period and data recording at the breeder's facility, the animals were transported for 2.25 h (Group 1) and for 7.5 h (Group 2) to a different animal facility. Data collection started immediately after arrival at the second animal facility. All parameters measured changed significantly after transport. These results suggest that a 10- to 12-day period is required for guineapigs to return to pre-transport levels of HR, BT and ACT. | 18,987,063 |
Characterization of cyanobacterial carotenoid ketolase CrtW and hydroxylase CrtR by complementation analysis in Escherichia coli. | The pathway from beta-carotene to astaxanthin is a crucial step in the synthesis of astaxanthin, a red antioxidative ketocarotenoid that confers beneficial effects on human health. Two enzymes, a beta-carotene ketolase (carotenoid 4,4'-oxygenase) and a beta-carotene hydroxylase (carotenoid 3,3'-hydroxylase), are involved in this pathway. Cyanobacteria are known to utilize the carotenoid ketolase CrtW and/or CrtO, and the carotenoid hydroxylase CrtR. Here, we compared the catalytic functions of CrtW ketolases, which originated from Gloeobacter violaceus PCC 7421, Anabaena (also known as Nostoc) sp. PCC 7120 and Nostoc punctiforme PCC 73102, and CrtR from Synechocystis sp. PCC 6803, Anabaena sp. PCC 7120 and Anabaena variabilis ATCC 29413 by complementation analysis using recombinant Escherichia coli cells that synthesized various carotenoid substrates. The results demonstrated that the CrtW proteins derived from Anabaena sp. PCC 7120 as well as N. punctiforme PCC 73102 (CrtW148) can convert not only beta-carotene but also zeaxanthin into their 4,4'-ketolated products, canthaxanthin and astaxanthin, respectively. In contrast, the Anabaena CrtR enzymes were very poor in accepting either beta-carotene or canthaxanthin as substrates. By comparison, the Synechocystis sp. PCC 6803 CrtR converted beta-carotene into zeaxanthin efficiently. We could assign the catalytic functions of the gene products involved in ketocarotenoid biosynthetic pathways in Synechocystis sp. PCC 6803, Anabaena sp. PCC 7120 and N. punctiforme PCC 73102, based on the present and previous findings. This explains why these cyanobacteria cannot produce astaxanthin and why only Synechocystis sp. PCC 6803 can produce zeaxanthin. | 18,987,067 |
Expressing positive emotions within online support groups by women with breast cancer. | Based upon Fredrickson's Broaden-and-Build Theory of Positive Emotions, this study examined the role of expressing positive emotions in online support groups for women with breast cancer. Underserved women with breast cancer in rural Wisconsin and Detroit, Michigan were recruited from 2001 to 2003, and they were given access to online support groups. Both pretest and four-month posttest surveys were conducted with a sample of 231 women. Messages from 96 active participants were analyzed using a computerized text analysis program. Psychological benefits that occurred following the expression of positive emotions were greater among those who expressed more negative emotions. | 18,987,072 |
The association of perceived partner-related social support with self-reported outcomes in women post-mastectomy. | Marital satisfaction is an important indicator of adaptation in patients with cancer; however, its relationship to medium-to-long-term health-related outcomes is less well understood. Married women (N = 152) at least six months post-mastectomy were surveyed to determine whether marital satisfaction predicted non-weight-related body image distress (BID), pain impact, and mood, or whether the directionality of this association operated in reverse. Structural equation modeling indicated that the model predicting medium-to-long-term health-related outcomes from satisfaction better fit the data and that time influences mood. | 18,987,076 |
Health risk perceptions as mediators of socioeconomic differentials in health behaviour. | Differentials in health status and behaviour by socioeconomic status (SES) constitute a scientific and policy challenge. In this article, data from a national survey on Canadians' perceptions of population health risks were analysed to determine whether various types of health risk perceptions mediated SES differentials in health behaviour. As expected, health behaviours and risk perceptions both varied with SES. Results suggested a mediating role of health risk perceptions-particularly those of a social nature-in the association between SES and smoking. Findings underscore the importance of improving the social environment to fostering better lifestyle and health among disadvantaged individuals. | 18,987,081 |
Clean intermittent self-catheterization in persons with multiple sclerosis: the influence of cognitive dysfunction. | Bladder problems are very common in persons with multiple sclerosis (PwMS). The aim of this study was to investigate the ability of PwMS to learn clean intermittent self-catheterization (CISC). The physical disability of 23 PwMS was evaluated with the Expanded Disability Status Scale (EDSS), and cognitive status was evaluated with the Brief Repeatable Battery of Neuropsychological Tests (BRB-N). CISC was taught by the same continence advisor who was blinded to the cognitive test results. The ability to learn CISC was evaluated immediately after sessions and 3 months later. Twenty-three consecutive PwMS participated in the study. In all, 87% (20/23) of the PwMS successfully finished CISC training. The number of lessons needed to acquire CISC skills differed significantly depending on the EDSS (Spearman r=0.682, P=0.0003), but the total cognitive decline subscore did not influence the ability to learn CISC. Only 13% (3/23) of the PwMS failed to learn CISC. The ability to learn CISC depended on the number of lessons needed to acquire CISC (r=-0.499, P=0.0313) and the EDSS score (r=-0.433, P=0.0390) but not on the course of the disease (r=0.125, P=0.5696) or on cognitive decline (r=-0.311, P=0.1480). After 3 months of follow-up, 30% (6/20) of the PwMS had ceased performing CISC. A follow-up indicated no statistically significant correlations among any of the subscores of the cognitive test battery, the EDSS score, the course of the disease, and the time required to learn CISC and effective bladder management. Our study thus confirmed that most (87%) PwMS were able to learn CISC in spite of cognitive dysfunction and therefore to improve their quality of life. | 18,987,108 |
Targeting renal macrophage accumulation via c-fms kinase reduces tubular apoptosis but fails to modify progressive fibrosis in the obstructed rat kidney. | The role of macrophages in promoting interstitial fibrosis in the obstructed kidney is controversial. Macrophage depletion studies in the unilateral ureter obstruction (UUO) model have produced opposing results, presumably reflecting the subtleties of the individual depletion methods used. To address this question, we targeted the macrophage colony-stimulating factor receptor, c-fms, which is uniquely expressed by cells of the monocyte/macrophage lineage. Administration of 5, 12.5, or 30 mg/kg (bid) of a selective inhibitor of c-fms kinase activity (fms-I) resulted in a dose-dependent inhibition of renal macrophage accumulation in the rat UUO model. This was due to inhibition of local macrophage proliferation in the obstructed kidney and, at higher doses, to depletion of circulating blood monocytes. To determine the contribution of macrophages to renal pathology in the obstructed kidney, groups of animals were treated with 30 mg/kg fms-I and killed 3, 7, or 14 days later. Complete inhibition of renal macrophage accumulation prevented upregulation of the macrophage-associated proinflammatory mediators, tumor necrosis factor (TNF)-alpha and matrix metalloproteinase-12, and significantly reduced tubular apoptosis. Macrophage depletion caused a minor reduction of interstitial myofibroblast accumulation and deposition of interstitial collagen IV at day 3, but no difference was seen in renal fibrosis on day 7 or 14. Similarly, the upregulation of collagen IV, fibronectin, transforming growth factor-beta1 and connective tissue growth factor mRNA levels on day 7 and 14 in the obstructed kidney was unaffected by macrophage depletion. In conclusion, c-fms blockade was shown to selectively prevent interstitial macrophage accumulation and to reduce tubular apoptosis in the obstructed kidney, but it had no significant impact on the development of interstitial fibrosis. | 18,987,110 |
Gaze pursuit responses in nucleus reticularis tegmenti pontis of head-unrestrained macaques. | Eye-head gaze pursuit-related activity was recorded in rostral portions of the nucleus reticularis tegmenti pontis (rNRTP) in alert macaques. The head was unrestrained in the horizontal plane, and macaques were trained to pursue a moving target either with their head, with the eyes stationary in the orbits, or with their eyes, with their head voluntarily held stationary in space. Head-pursuit-related modulations in rNRTP activity were observed with some cells exhibiting increases in firing rate with increases in head-pursuit frequency. For many units, this head-pursuit response appeared to saturate at higher frequencies (>0.6 Hz). The response phase re:peak head-pursuit velocity formed a continuum, containing cells that could encode head-pursuit velocity and those encoding head-pursuit acceleration. The latter cells did not exhibit head position-related activity. Sensitivities were calculated with respect to peak head-pursuit velocity and averaged 1.8 spikes/s/deg/s. Of the cells that were tested for both head- and eye-pursuit-related activity, 86% exhibited responses to both head- and eye-pursuit and therefore carried a putative gaze-pursuit signal. For these gaze-pursuit units, the ratio of head to eye response sensitivities averaged approximately 1.4. Pursuit eccentricity seemed to affect head-pursuit response amplitude even in the absence of a head position response per se. The results indicated that rNRTP is a strong candidate for the source of an active head-pursuit signal that projects to the cerebellum, specifically to the target-velocity and gaze-velocity Purkinje cells that have been observed in vermal lobules VI and VII. | 18,987,125 |
Intrafamilial transmission and family-specific spectra of cutaneous betapapillomaviruses. | Cutaneous human betapapillomaviruses (beta-HPVs) are widespread in the general population and have been associated with skin cancer. To evaluate the impact of continuous person-to-person contact within families on an individual's beta-HPV type spectrum, we collected serial skin swab samples from parents and children from 10 families. All participants were found to be beta-HPV DNA positive, with 1 to 13 types at study entry (median, 4.0 types). Initial and cumulative (2 to 16 types) HPV type multiplicities varied widely between different families but only a little between family members. The high intrafamilial correlation of HPV multiplicity is already obvious for babies aged 10 days to 10 months. Family members typically displayed similar spectra of HPV types. More than 75% of the HPV types in babies were also detected in their parents. This indicates that HPV transmission mainly results from close contact between family members. Type-specific persistence for at least 9 months was more prevalent in parents (92%) than in children (66%). Of the types detected throughout the study, 24% turned out to persist in the parents and only 11% in the children. Interestingly, about one-half of the HPV types found to persist in one of the parents occurred less frequently or even only sporadically in the spouse. Similarly, only one-third of the persisting parental types also persisted in their children. This indicates that even regular exposure to cutaneous HPV does not necessarily lead to the establishment of a persistent infection, which may point to type-specific susceptibilities of different individuals. | 18,987,132 |
Differential CD4+ T-lymphocyte apoptosis and bystander T-cell activation in rhesus macaques and sooty mangabeys during acute simian immunodeficiency virus infection. | In contrast to pathogenic lentiviral infections, chronic simian immunodeficiency virus (SIV) infection in its natural host is characterized by a lack of increased immune activation and apoptosis. To determine whether these differences are species specific and predicted by the early host response to SIV in primary infection, we longitudinally examined T-lymphocyte apoptosis, immune activation, and the SIV-specific cellular immune response in experimentally infected rhesus macaques (RM) and sooty mangabeys (SM) with controlled or uncontrolled SIV infection. SIVsmE041, a primary SIVsm isolate, reproduced set-point viremia levels of natural SIV infection in SM but was controlled in RM, while SIVmac239 replicated to high levels in RM. Following SIV infection, increased CD8(+) T-lymphocyte apoptosis, temporally coinciding with onset of SIV-specific cellular immunity, and elevated plasma Th1 cytokine and gamma interferon-induced chemokine levels were common to both SM and RM. Different from SM, SIV-infected RM showed a significantly higher frequency of peripheral blood activated CD8(+) T lymphocytes despite comparable magnitude of the SIV-specific gamma interferon enzyme-linked immunospot response. Furthermore, an increase in CD4(+) and CD4(-)CD8(-) T-lymphocyte apoptosis and plasma tumor necrosis factor-related apoptosis-inducing ligand were observed only in RM and occurred in both controlled SIVsmE041 and uncontrolled SIVmac239 infection. These data suggest that the "excess" activated T lymphocytes in RM soon after SIV infection are predominantly of non-virus-specific bystander origin. Thus, species-specific differences in the early innate immune response appear to be an important factor contributing to differential immune activation in natural and nonnatural hosts of SIV infection. | 18,987,149 |
Genome analysis of small-ruminant lentivirus genotype E: a caprine lentivirus with natural deletions of the dUTPase subunit, vpr-like accessory gene, and 70-base-pair repeat of the U3 region. | The nucleotide sequence of the highly divergent small-ruminant lentivirus genotype E has been determined. The full genome consists of 8,418 nucleotides and lacks two large portions corresponding nearly to the entire dUTPase subunit of the pol and vpr-like accessory genes. Moreover, the 70-bp repeat of the U3 region of the long terminal repeat was observed to be deleted. Interestingly, this lentivirus genotype is able to persist in a local breed population, and retrospective analysis revealed its presence in milk samples collected in 1999. gag sequences obtained from a flock coinfected with the B1 and E genotypes revealed that the evolutionary rates of the two viruses were quite similar. Since a reduced viral load and/or disease progression was observed for viruses with artificially deleted dUTPase and vpr-like genes, it is proposed that this viral cluster be designated a low-pathogenicity caprine lentivirus. | 18,987,157 |
Flagellin-F1-V fusion protein is an effective plague vaccine in mice and two species of nonhuman primates. | A number of studies have clearly demonstrated that flagellin is a potent adjuvant that promotes robust immune responses when it is given with a protein antigen. In view of the potential biological and practical benefits of a recombinant protein vaccine composed of a single fusion protein containing flagellin and antigen, we have evaluated the efficacy of a fusion protein composed of flagellin and two protective antigens of Yersinia pestis (F1 and V) in eliciting protection against respiratory challenge with Y. pestis. Flagellin-F1-V was produced and purified in high yield under good manufacturing practices conditions. The fusion protein retains full Toll-like receptor 5-stimulating activity in vitro. Using a prime-boost immunization protocol, we found that flagellin-F1-V elicits robust antigen-specific humoral immunity in mice and two species of nonhuman primates. Immune mice were fully protected against intranasal challenge with 150 mean tolerated doses of Y. pestis CO92. In immune mice, the bacteria were completely cleared within 3 days after challenge. Flagellin-F1-V exhibited full stability for at least 297 days at 4 degrees C and at least 168 days at 25 degrees C. At between 29 and 84 days at 37 degrees C, the protein exhibited a loss of biological activity that appeared to be associated with a substantial change in protein diameter, possibly due to oligomerization. On the basis of our results, we believe that flagellin-F1-V is an outstanding candidate for evaluation in studies with humans. | 18,987,167 |
Sporadic hypercalcitoninemia: clinical and therapeutic consequences. | 'Calcitonin screening' is not accepted as the standard of care in daily practice. The clinical and surgical consequences of 'calcitonin screening' in a series of patients with mildly elevated basal calcitonin and pentagastrin stimulated calcitonin levels are presented. 260 patients with elevated basal (>10 pg/ml) and stimulated calcitonin levels (>100 pg/ml) were enrolled in this prospective study. None of the patients was member of a known medullary thyroid carcinoma family. Thyroidectomy and bilateral central and lateral neck dissections were performed. Testing for the presence of germ-line mutations was performed in all patients. Histological and immunohistochemical findings were compared with basal and stimulated calcitonin levels. All patients were subsequently followed biochemically. C-cell hyperplasia (CCH) was found in 126 (49%) and medullary thyroid cancer was found in 134 (51%) patients. RET proto-oncogen mutations were documented in 22 (8%) patients (medullary thyroid cancer:18, CCH:4). In 56 (46%) of 122 patients, sporadic CCH was classified neoplastic ('carcinoma in situ'). Of 97 (72%; 10 with hereditary medullary thyroid cancer) had pT1 (International Union against Cancer recommendations 2002) and 33 (25%) had pT2 or pT3 and 4 (3%) pT4 tumors. Of 39 (29.1%) had lymph node metastases. 106 (79.1%; 15 (38.5%) with lymph node metastases) patients were cured. Evaluation of basal and stimulated calcitonin levels enables the prediction of medullary thyroid cancer. All patients with basal calcitonin >64 pg/ml and stimulated calcitonin >560 pg/ml have medullary thyroid cancer. Medullary thyroid cancer was documented in 20% of patients with basal calcitonin >10 pg/ml but <64 pg/ml and stimulated calcitonin >100 pg/ml but <560 pg/ml. | 18,987,170 |
Identification of Candida albicans and Candida glabrata within 1.5 hours directly from positive blood culture bottles with a shortened peptide nucleic acid fluorescence in situ hybridization protocol. | Candida albicans and Candida glabrata can be identified in blood culture bottles within 2.5 h using peptide nucleic acid fluorescence in situ hybridization. A 1.25-h protocol was compared to the standard with 40 positive (clinical and spiked) blood culture bottles tested in batches of 5. All C. albicans (15) and C. glabrata (16) isolates, alone or mixed, were identified correctly using both protocols, whereas 18 isolates (five other species) were negative by both protocols. This shortened method will significantly reduce the time to identification. | 18,987,173 |
Stepwise diagnosis of Trichomonas vaginalis infection in adolescent women. | The objective of this study was to examine the effects of clinical factors and of the type and timing of a secondary test in improving the sensitivity of Trichomonas vaginalis detection in young women over that of a wet mount alone. For this purpose, sexually active adolescent women (n = 345) were recruited from a hospital teen clinic or emergency department. Following an interview and a pelvic exam, four primary T. vaginalis tests (wet mount, culture, a rapid test, and a nucleic acid amplification test [NAAT]) were performed on vaginal swabs. If the wet-mount result was negative, two secondary tests (culture and a rapid test) were performed on the used wet-mount swab and saline. A positive result by any of the four primary tests was considered a true T. vaginalis-positive result. The prevalence of T. vaginalis was 18.8% overall and 8.8% in the 307 wet-mount-negative women. There was 100% concordance between primary and secondary rapid tests. Secondary culture was 80% sensitive compared to primary culture. The likelihood of a positive rapid test increased with increasing time between specimen collection and testing. A wet mount followed by a rapid test was the most sensitive strategy using two tests (86.4%; confidence interval [CI], 75.3 to 93.4%). Limiting secondary testing to those with multiple partners resulted in a lower sensitivity (73.9%; CI, 61.5 to 84%) that was not significantly better than that of the wet mount alone (58.5%; CI, 45.6 to 70.6%). We conclude that a rapid test can be delayed or performed on a used swab with no loss of sensitivity. Until a NAAT for T. vaginalis is commercially available, a stepwise approach using an additional rapid test for wet-mount-negative women is recommended for adolescent women regardless of clinical factors. | 18,987,174 |
Chelation of mitochondrial iron prevents seizure-induced mitochondrial dysfunction and neuronal injury. | Chelatable iron is an important catalyst for the initiation and propagation of free radical reactions and implicated in the pathogenesis of diverse neuronal disorders. Studies in our laboratory have shown that mitochondria are the principal source of reactive oxygen species production after status epilepticus (SE). We asked whether SE modulates mitochondrial iron levels by two independent methods and whether consequent mitochondrial dysfunction and neuronal injury could be ameliorated with a cell-permeable iron chelator. Kainate-induced SE resulted in a time-dependent increase in chelatable iron in mitochondrial but not cytosolic fractions of the rat hippocampus. Systemically administered N,N'-bis (2-hydroxybenzyl) ethylenediamine-N,N'-diacetic acid (HBED), a synthetic iron chelator, ameliorated SE-induced changes in chelatable iron, mitochondrial oxidative stress (8-hydroxy-2' deoxyguanosine and glutathione depletion), mitochondrial DNA integrity and hippocampal cell loss. Measurement of brain HBED levels after systemic administration confirmed its penetration in hippocampal mitochondria. These results suggest a role for mitochondrial iron in the pathogenesis of SE-induced brain damage and subcellular iron chelation as a novel therapeutic approach for its management. | 18,987,191 |
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