title stringlengths 0 1.13k | abstract stringlengths 1 15.7k | PMID int64 22 36.5M |
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Engineering tandem modular protein based reversible hydrogels. | We report the engineering of the first tandem modular protein based hydrogel that exhibits unique properties combining low erosion rate, fast and reversible sol-gel transition and antibody binding ability. | 18,802,510 |
Facile one pot synthesis of a range of reversible addition-fragmentation chain transfer (RAFT) agents. | The application of a universal synthetic strategy for the high yielding and facile synthesis of a wide range of functional RAFT agents including trithiocarbonates, xanthates and dithiocarbamates is described. | 18,802,523 |
Chemogenetic protein engineering: an efficient tool for the optimization of artificial metalloenzymes. | Artificial metalloenzymes, based on the incorporation of a catalytically active organometallic moiety within a host protein, lie at the interface between organometallic and enzymatic catalysis. In terms of activity, reaction repertoire, substrate range and operating conditions, they take advantage of the versatility of the organometallic chemistry. In contrast, the enantioselectivity is determined by the biomolecular scaffold, which provides a well defined second coordination sphere to the organometallic moiety, reminiscent of enzymes. The attractive feature of such systems is their optimization potential, which combines chemical and genetic methods (i.e. chemogenetic) to screen diversity space. This feature article describes the implementation of such an optimization protocol for artificial transfer hydrogenases, for which we have the most detailed understanding. | 18,802,535 |
Activatable imaging probes with amplified fluorescent signals. | Current optical imaging probe applications are hampered by poor sensitivity and specificity to the target, but molecular-level fluorescent signal activation strategies can efficiently overcome these limitations. Recent interdisciplinary research that couples the imaging sciences to fluorophore, peptide, polymer, and inorganic-based chemistry has generated novel imaging probes that exhibit high sensitivity and low background noise in both in vitro and in vivo applications. This feature article introduces and discusses the various approaches described by the term "fluorescent signal activation methods" with respect to their unique imaging probe design strategies and applications. | 18,802,536 |
Diol-substituted boron complexes of dipyrrolyl diketones as anion receptors and covalently linked 'pivotal' dimers. | Diol-substitution at a boron unit results in the formation of anion receptors consisting of dipyrrolyl diketones and covalently linked dimers, which exhibit selective binding for dianions with appropriate lengths. | 18,802,545 |
Ni(II)-catalyzed enantioselective Nazarov cyclizations. | Nazarov cyclizations are catalyzed by a dicationic Ni(II) complex containing the chiral tridentate phosphine Pigiphos; the catalyst exerts a high degree of torquoselectivity and affords the products in up to 88% ee. | 18,802,555 |
Unusual temperature dependence of salt effects for "on water" Wittig reaction: hydrophobicity at the interface. | An unusual variation with temperature of the salt effects in aqueous Wittig reaction is observed, suggesting that hydrophobic acceleration of reactions comprising "on water" reactants is fundamentally different from that for reactions with small non-polar solutes. | 18,802,585 |
Ultra stable ordered mesoporous phenol/formaldehyde polymers as a heterogeneous support for vanadium oxide. | Ordered mesoporous phenol/formaldehyde polymers are presented as an ultra stable heterogeneous support for vanadium oxide. | 18,802,595 |
Extraction behavior of lanthanides using a diglycolamide derivative TODGA in ionic liquids. | Liquid-liquid extraction of lanthanides from aqueous solutions into ionic liquids (ILs) has been investigated using N,N,N',N'-tetra(n-octyl)diglycolamide (TODGA) as an extractant, and compared with that in the isooctane system. Application of ILs as the extracting phase provided unprecedented enhancement of the extraction performance of TODGA for lanthanides compared with that of the isooctane system. Slope analysis confirmed that TODGA in ILs formed a 1:3 complex with La3+, Eu3+, or Lu3+. On the other hand, the molar ratios of species extracted into isooctane were 1:3 for La3+ or 1:4 for Eu3+ and Lu3+, depending on the atomic number of the lanthanide. The transfer of lanthanides with TODGA into ILs proceeded via a cation-exchange mechanism, in contrast to ion pair extraction in the isooctane system. Furthermore, we clarified that TODGA provided selectivity for the middle lanthanides in the ILs systems, but heavier lanthanides in the isooctane system. | 18,802,624 |
Amine and ammonium functionalization of chloromethylsilane-ended dendrimers. Antimicrobial activity studies. | Novel amine- and ammonium-terminated carbosilane dendrimers of type G(n)-[Si{CH(2)O-(C(6)H(4))-3-NMe(2)}](x) or G(n)-[Si{CH(2)O-(C(6)H(4))-3-NMe(3)(+)I(-)}](x) have been synthesized and characterized up to second generation by phenolysis of (chloromethyl)silyl-terminated dendrimers with 3-dimethylamine phenol and subsequent quaternization with methyl iodide. Quaternized carbosilane dendrimers are stable in protic solvents and can be solubilised in water after the addition of less than 1% of dimethyl sulfoxide. A study of the antimicrobial activity of these cationic dendrimers of first and second generation against both gram-positive and gram-negative bacteria is also described. The results obtained demonstrate that the new ammonium-terminated carbosilane dendrimers can be considered as multivalent biocides. | 18,802,631 |
Synthetic tetra-acylated derivatives of lipid A from Porphyromonas gingivalis are antagonists of human TLR4. | Tetra-acylated lipid As derived from Porphyromonas gingivalis LPS have been synthesized using a key disaccharide intermediate functionalized with levulinate (Lev), allyloxycarbonate (Alloc) and anomeric dimethylthexylsilyl (TDS) as orthogonal protecting groups and 9-fluorenylmethoxycarbamate (Fmoc) and azido as amino protecting groups. Furthermore, an efficient cross-metathesis has been employed for the preparation of the unusual branched R-(3)-hydroxy-13-methyltetradecanic acid and (R)-3-hexadecanoyloxy-15-methylhexadecanoic acid of P. gingivalis lipid A. Biological studies have shown that the synthetic lipid As cannot activate human and mouse TLR2 and TLR4 to produce cytokines. However, it has been found that the compounds are potent antagonist of cytokine secretion by human monocytic cells induced by enteric LPS. | 18,802,645 |
Lithium dilution cardiac output measurement in the critically ill patient: determination of precision of the technique. | Lithium dilution cardiac output by LiDCOplus (LiDCO, Cambridge, UK) is a validated methodology for measuring cardiac output. It is used to calibrate a pulse pressure analysis algorithm (PulseCO) for the continuous measurement of subsequent changes in this variable. The variability of measurements, or precision, within patients of lithium dilution cardiac output has not previously been described. Thirty-five hemodynamically stable patients in intensive care, with no significant variability in heart rate, mean arterial pressure or central venous pressure, were recruited. Fifty-three determinations of cardiac output were made, each using four lithium dilution measurement curves performed consecutively within a maximum period of 10 min. The coefficient of variation of the measurements was determined and used to derive the least significant change in cardiac output that this technique could reliably detect. For a single measurement, the coefficient of variation was 8%. This equates to the technique being able to detect a change (least significant change) between two measurements of 24%. Averaging two lithium dilution measurements improved the coefficient of variation to 6% with a least significant change of 17%. Using the average of three curves reduced the coefficient of variation to 5% with a least significant change of 14%. To achieve a good precision with this technique, three lithium dilution measurements should be averaged. This will allow changes in cardiac output of more than 14% to be reliably detected. The understanding of the precision of this technique allows the user to know when a real change has happened to their patient. | 18,802,681 |
Chronic sleep disorders in survivors of the acute respiratory distress syndrome. | Sleep disruption is well recognized in the Intensive Care Unit. Poor sleep quality likely continues following discharge from hospital in several patients and becomes a chronic disorder in some. The aim of this study was to describe the etiology of chronic sleep complaints in survivors of ARDS. Seven ARDS survivors with no previous sleep complaints who reported difficulty sleeping 6 months or more following discharge from hospital were evaluated. Sleep quality was assessed subjectively with a sleep history and the Insomnia Severity Index and objectively with polysomnography. Daytime sleepiness was assessed with the Epworth Sleepiness Scale. A chronic sleep disorder was identified in each patient who reported difficulty sleeping. The primary sleep disorder was chronic conditioned insomnia (5 patients), parasomnia (1 patient) and obstructive sleep apnea (1 patient). In addition, 4 patients had periodic leg movements, which was of uncertain clinical significance. Chronic sleep disorders, which originate during the acute illness, are present in some ARDS survivors several months after discharge from hospital. If unrecognized, lack of treatment may contribute to impaired quality of life and incomplete rehabilitation from their critical illness. | 18,802,684 |
Hyper production of cellulase-free xylanase by Thermomyces lanuginosus SSBP on bagasse pulp and its application in biobleaching. | A cellulase-free xylanase production by Thermomyces lanuginosus SSBP using bagasse pulp was examined under submerged (SmC) and solid-state cultivation (SSC). Higher level of xylanase activity (19,320 +/- 37 U g(-1) dried carbon source) was obtained in SSC cultures than in SmC (1,772 +/- 15 U g(-1) dried carbon source) after 120 h with 10% inoculum. The biobleaching efficacy of crude xylanase was tested on bagasse pulp, and the maximum brightness of 46.1 +/- 0.06% was observed with 50 U of crude xylanase per gram of pulp, which was 3.8 points higher than the brightness of untreated samples. Reducing sugars (26 +/- 0.1 mg g(-1)) and UV-absorbing lignin-derived compounds in the pulp filtrates were observed as maximum in 50 U of crude xylanase-treated samples. T. lanuginosus SSBP has potential applications due to its high productivity of xylanase and its efficiency in pulp bleaching. | 18,802,693 |
Cloning and functional characterization of a complex endo-beta-1,3-glucanase from Paenibacillus sp. | A beta-1,3-glucanase gene, encoding a protein of 1,793 amino acids, was cloned from a strain of Paenibacillus sp. in this study. This large protein, designated as LamA, consists of many putative functional units, which include, from N to C terminus, a leader peptide, three repeats of the S-layer homologous module, a catalytic module of glycoside hydrolase family 16, four repeats of the carbohydrate-binding module of family CBM_4_9, and an analogue of coagulation factor Fa5/8C. Several truncated proteins, composed of the catalytic module with various organizations of the appended modules, were successfully expressed and characterized in this study. Data indicated that the catalytic module specifically hydrolyze beta-1,3- and beta-1,3-1,4-glucans. Also, laminaritriose was the major product upon endolytic hydrolysis of laminarin. The CBM repeats and Fa5/8C analogue substantially enhanced the hydrolyzing activity of the catalytic module, particularly toward insoluble complex substrates, suggesting their modulating functions in the enzymatic activity of LamA. Carbohydrate-binding assay confirmed the binding capabilities of the CBM repeats and Fa5/8C analogue to beta-1,3-, beta-1,3-1,4-, and even beta-1,4-glucans. These appended modules also enhanced the inhibition effect of the catalytic module on the growth of Candida albicans and Rhizoctonia solani. | 18,802,694 |
Low representation of Fc receptor-like 1-5 molecules in leukemic cells from Iranian patients with acute lymphoblastic leukemia. | Recent studies have demonstrated expression of Fc receptor-like (FCRL) molecules, a newly identified family with preferential B-cell lineage expression, in some chronic B-cell leukemias with possible implication for classification and/or targeted immunotherapy. In this study, the expression pattern of FCRL1-5 genes was studied in 73 Iranian ALL patients and 35 normal subjects using semi-quantitative RT-PCR method. FCRL protein expression was also investigated by flow cytometry. Our results indicate significant down-regulation of all FCRL genes in ALL compared to normal subjects. Although, FCRL mRNA expression was almost exclusively confined to normal isolated B-cells compared to T-cells, but these genes were similarly expressed in B-ALL, T-ALL and different B-ALL immunophenotypic subtypes. Surface protein expression of FCRL1, 2, 4, and 5 molecules in 10 ALL and 5 normal samples confirmed the PCR results. Expression profile of FCRL molecules in different subtypes of ALL argues against their potential implication as suitable targets for classification and/or immunotherapy of ALL. | 18,802,695 |
Paclitaxel reduces regulatory T cell numbers and inhibitory function and enhances the anti-tumor effects of the TLR9 agonist PF-3512676 in the mouse. | The anti-tumor properties of Toll-like receptor (TLR) 9 agonist CpG oligodeoxynucleotides (ODN) are enhanced by combinations with several cytotoxic chemotherapy regimens. The mechanisms of this added benefit, however, remain unclear. We now report that, similar to the depletion of regulatory T cells (Treg) using anti-CD25, paclitaxel increased the anti-tumor effect of the TLR9 agonist PF-3512676 in a CD8(+) T cell-dependent fashion. Paclitaxel treatment decreased Treg numbers in a TLR4-independent fashion, and preferentially affected cycling Treg expressing high levels of FoxP3. The paclitaxel-induced reduction in Treg FoxP3 expression was associated with reduced inhibitory function. Adoptively transferred tumor-antigen specific CD8(+) T cells proliferated better in mice treated with paclitaxel and their recruitment in the tumor was increased. However, the systemic frequency of PF-3512676-induced tumor-antigen specific effector CD8(+) T cells decreased with paclitaxel, suggesting opposite effects of paclitaxel on the anti-tumor response. Finally, gene expression profiling and studies of tumor-associated immune cells revealed a complex modulation of the PF-3512676-induced immune response by paclitaxel, including a decrease of IL-10 expression and an increase in IL-17-secreting CD4(+) T cells. Collectively, these data suggest that paclitaxel combined with PF-3512676 may not only promote a better anti-tumor CD8(+) response though increased recruitment in the tumor, possibly through Treg depletion and suppression, but also exerts more complex immune modulatory effects. | 18,802,696 |
High expression of PGE2 enzymatic pathways in cervical (pre)neoplastic lesions and functional consequences for antigen-presenting cells. | Although human papillomavirus (HPV) DNA is detected in the majority of squamous intraepithelial lesions (SIL) and carcinoma (SCC) of the uterine cervix, the persistence or progression of cervical lesions suggest that viral antigens are not adequately presented to the immune system. This hypothesis is reinforced by the observation that most SIL show quantitative and functional alterations of Langerhans cells (LC). The aim of this study was to determine whether prostaglandins (PG) may affect LC density in the cervical (pre)neoplastic epithelium. We first demonstrated that the epithelial expression of PGE(2) enzymatic pathways, including cyclooxygenase-2 (COX-2) and microsomal prostaglandin E synthase 1 (mPGES-1), is higher in SIL and SCC compared to the normal exocervical epithelium and inversely correlated to the density of CD1a-positive LC. By using cell migration assays, we next showed that the motility of immature dendritic cells (DC) and DC partially differentiated in vitro in the presence of PGE(2) are differentially affected by PGE(2). Immature DC had a lower ability to migrate in the presence of PGE(2) compared to DC generated in vitro in the presence of PGE(2). Finally, we showed that PGE(2) induced a cytokine production profile and phenotypical features of tolerogenic DC, suggesting that the altered expression of PGE(2) enzymatic pathways may promote the cervical carcinogenesis by favouring (pre)cancer immunotolerance. | 18,802,697 |
Dermatomyositis associated with hepatitis B virus-related hepatocellular carcinoma. | Dermatomyositis (DM) is an idiopathic inflammatory myopathy (IIM) with typical cutaneous manifestations. It has been proposed that DM may be caused by autoimmune responses to viral infections, and previous studies have also shown that an association between DM and malignancy. However, chronic hepatitis B virus (HBV) infection associated with DM and hepatocellular carcinoma (HCC) is rarely encountered. The authors report a case of DM and HCC in a patient with a HBV infection. A 58-year-old man presented erythematous skin rashes on a sun-exposed area of 2 year's duration, and recent proximal muscle weakness. His medical history revealed that he had a chronic HBV infection. A diagnosis of DM relies on proximal muscle weakness, elevated muscle enzymes, myopathic changes (demonstrated by electromyography), muscle biopsy evidence of myositis, and its characteristic cutaneous findings. A Liver mass in the left lobe visualized by abdominal computed tomography was confirmed histologically as HCC. This case suggests that DM associated with HCC might be caused by a HBV infection. | 18,802,699 |
Drug resistance and genetic mapping in Plasmodium falciparum. | Drug resistance in malaria parasites is a serious public health burden, and resistance to most of the antimalarial drugs currently in use has been reported. A better understanding of the molecular mechanisms of drug resistance is urgently needed to slow or circumvent the spread of resistance, to allow local treatments to be deployed more effectively to prolong the life span of the current drugs, and to develop new drugs. Although mutations in genes determining resistance to drugs such as chloroquine and the antifolates have been identified, we still do not have a full understanding of the resistance mechanisms, and genes that contribute to resistance to many other drugs remain to be discovered. Genetic mapping is a powerful tool for the identification of mutations conferring drug resistance in malaria parasites because most drug-resistant phenotypes were selected within the past 60 years. High-throughput methods for genotyping large numbers of single nucleotide polymorphisms (SNPs) and microsatellites (MSs) are now available or are being developed, and genome-wide association studies for malaria traits will soon become a reality. Here we discuss strategies and issues related to mapping genes contributing to drug resistance in the human malaria parasite Plasmodium falciparum. | 18,802,698 |
Tissue expression pattern of class II and class V genes found in the Adh complex on mouse chromosome 3. | The alcohol dehydrogenase enzymes in mice and humans are encoded by a linked group of genes in the same transcriptional orientation. The enzymes play important roles in alcohol metabolism and retinoid signaling and homeostasis. The expression patterns at the mRNA level of the mouse Adh4 (class II) gene and the recently identified Adh6a and Adh6b genes (class V) are now reported to complete this analysis for the entire family. Adh4 is expressed at high levels in liver and is detectable in small intestine and testes. Adh6b is expressed in liver but Adh6a is not. Adh6a is expressed at high levels in small intestine while Adh6b is not. Adh6a expression is detectable in the female adrenal and not at all in the male adrenal, but Adh6b is expressed at moderate levels in both sexes. Although Adh6a and Adh6b have expression patterns different from each other, neither expresses like any other gene in the complex, suggesting different control mechanisms and possibly different functions. | 18,802,746 |
The influence of a toxic cyanobacterial bloom and water hydrology on algal populations and macroinvertebrate abundance in the upper littoral zone of Lake Krugersdrift, South Africa. | The biological interactions and the physical and chemical properties of the littoral zone of Lake Krugersdrift were studied for a 4-month period when a dense, toxic cyanobacterial bloom dominated by Microcystis aeruginosa was present in the main lake basin. The presence of a toxic strain of M. aeruginosa was confirmed through the use of ELISA and molecular markers that detect the presence of the mcyB and mcyD genes of the mcy gene cluster that synthesizes microcystin. An increase in Microcystis toxicity at sites dominated by the cyanobacterial scum was accompanied by an increase in total abundance of the macroinvertebrate families Hirudinae, Chironomidae, and Tubificidae. Sites located away from the cyanobacterial scum had a lower abundance but a higher diversity of macroinvertebrates. The water quality under the Microcystis scum was characterized by low pH values, low concentrations of dissolved oxygen, and lower total alkalinity values. The periphytic alga Ulothrix zonata was absent in areas dominated by the cyanobacterial scum, possibly as a result of overshadowing by the scum or direct toxic allelopathic effects on growth and photosynthesis. The diatom Diatoma vulgare dominated the benthic algal flora beneath the cyanobacterial scum. | 18,802,748 |
Protein kinase C regulates the expression of M1 receptors and BDNF in rat retinal cells. | Protein kinase C (PKC) plays a key role in cellular events including proliferation, survival and differentiation. Our previous study showed the effect of phorbol 12-myristate 13-acetate (PMA), a PKC activator, inducing a decrease in retinal cells proliferation. This effect was mediated by muscarinic type 1 receptors (M1) activation and brain derived neurotrophic factor (BDNF) treatment also induced a decrease in cell proliferation. Based on these results we analyzed the expression of either M1 receptors or BDNF following PMA treatment of retinal cell cultures. Our data demonstrated that PMA induced a decrease in both protein expressions after 48 h in culture. However, after 45 min, PMA induced a transient increase in BDNF expression and a decrease in M1 receptors expression. Analyzing the expression of M1 receptors and BDNF during the postnatal development in vivo, we observed a decrease in both proteins. Taken together our results suggest the involvement of PKC in the control of M1 expression in retinal cells. | 18,802,750 |
Immunocytochemical detection of neuronal NO synthase in rat brain cells. | The aims of the present work were to identify the neuronal form of nitric oxide synthase (nNOS type I) in brain structures in rats by immunocytochemistry, to compare the results with data from histochemical reactions for NADPH-diaphorase, and to develop the optimal conditions for fixation for detecting nNOS. The product of the histochemical reaction was found to be located strictly in the cytoplasm. Immunocytochemical detection of nNOS showed that along with the cytoplasmic reaction for nNOS, the nuclei of some neurons and gliocytes were immunopositive, though the cytoplasm of these cells gave negative reactions for nNOS. Selection of the optimal fixation conditions for specimens and the dilution of the primary antibody allowed reductions in the intensity of nuclear nNOS-type reactions without affecting the specific reaction of the cytoplasm for nNOS. These data provide evidence that the best detection of nNOS in paraffin sections is obtained using immersion fixation in Carnoy's fluid or post-fixation in this solution after perfusion with 4% paraformaldehyde. | 18,802,756 |
Experience in the use of Actovegin in the treatment of patients with cognitive disorders in the acute period of stroke. | Forty-three patients with mild-moderate ischemic stroke were studied in the acute period and were divided into two groups. The experimental group consisted of 32 patients who were given Actovegin; the reference group consisted of 11 patients who were given piracetam. Patients were investigated before treatment and at 10 and 30 days; investigations included examination, points assessments of neurological disorders using the original Gusev-Skvortsova scale, neuropsychological tests using the MMSE scale, rheoencephalography, and electroencephalography. Analysis of changes in clinical features in patients treated with Actovegin during the acute period showed that Actovegin had clear positive effects both on general cerebral and on focal neurological symptoms. By the end of treatment, the extent of recovery of impaired functions, assessed in terms of total ischemic points and cognitive functions, was significantly greater in patients treated with Actovegin than in patients given piracetam. These data lead to the conclusion that Actovegin is effective in the treatment of patients with ischemic stroke. | 18,802,768 |
Immunohistochemical study concerning the origin of neurocytoma--a case report. | A 26-year-old woman presented with rapid tumor growth in her left frontal lobe during 9 years of observation. Operative findings revealed a massive tumor connected to gelatinous, transparent membranous tissue (MT), which extended from the paraventricular zone and continued into the lateral ventricle. Histological diagnosis was atypical neurocytoma. Immunohistochemical analyses revealed that the tumor was strongly positive for not only neural markers but also a glial marker, while the MT was positive for a neural marker. The Ki-67/MIB-1 labeling index was 9.1% in the tumor body and 0% in the MT. Musashi 1, a marker of neural stem cells, was strongly positive in both the tumor body and the MT. We speculate that the tumor growth was due to a rapid decline of the Musashi 1-positive cells to glial differentiation. These cells may be candidates for the origin of the tumor. | 18,802,789 |
Heterogeneity of prostate-specific membrane antigen (PSMA) expression in prostate carcinoma with distant metastasis. | Prostate-specific membrane antigen (PSMA) is a transmembrane protein that is overexpressed in advanced stage prostate adenocarcinomas. As a novel target for in vivo prognostic and therapeutic approaches, the distribution pattern of PSMA in primary and metastatic tumors is of significant interest. In this study we addressed the cellular distribution and heterogeneity of PSMA expression. Paraffin-embedded sections of 51 patients with primary prostate carcinoma and distant metastases were evaluated. Immunohistochemistry was used to determine the cellular localization, staining intensity and positive cell fraction which were related to tumor type and growth pattern. We demonstrated differences in the intracellular localization of the PSMA immunostaining which seem to be related to the tumor differentiation pattern. A significant number of the primary tumors (7/51) and metastases (6/51) presented with highly heterogeneous PSMA expression and in further 2 primary, and 8 metastatic tumors the staining was in the negative range (<10% positive tumor cells). A direct correlation between histological parameters and PSMA expression could not be demonstrated. Our findings clearly support the feasibility but also direct to potential failures of PSMA-targeted in vivo diagnostic and therapeutic approaches in prostate cancer patients with distant metastasis. | 18,802,790 |
Haplotypic diversity within the ovine calpastatin (CAST) gene. | Calpastatin (CAST) is a protein inhibitor that acts specifically on calpains and plays a regulatory role in postmortem beef tenderization and muscle proteolysis. Polymorphisms in the bovine CAST gene have been associated with meat tenderness, but little is known about how the ovine CAST gene may affect sheep meat quality traits. In this study, we selected two parts of the ovine CAST gene that have been previously reported to be polymorphic (region 1-part of intron 5 and exon 6, and region 2-part of intron 12), to investigate haplotype diversity across an extended region of the ovine gene. First, we developed a simple and efficient polymerase chain reaction-single-strand conformational polymorphism (PCR-SSCP) method for genotyping region 2, which allowed the detection of a novel allele as well as the three previously reported alleles. Next, we genotyped both regions 1 and 2 of the ovine CAST gene from a large number of sheep to determine the haplotypes present. Nine different haplotypes were found across this extended region of the ovine CAST gene and four haplotypes were identified that suggested historical recombination events within this gene. Haplotypes are typically more informative than single nucleotide polymorphisms (SNPs) for analyzing associations between genes and complex production traits, such as meat tenderness, but the potential for intragenic recombination within the ovine CAST may make finding associations challenging. | 18,802,795 |
[Frontotemporal lobar degeneration: a descriptive study of 42 patients]. | Frontotemporal lobar degeneration (FTLD) is considered to be the second cause of presenile dementia. In spite of the great interest it has generated over the last few years, few studies have been published in our country. A descriptive retrospective study of 42 patients with FTLD evaluated in our unit during the period 1996-2006 was performed. Thirty one patients presented with frontal variant FTLD (FTD), eigth with non-fluent progressive aphasia and three with semantic dementia. Mean age at onset was 56 years, diagnostic delay 3.5 years and mean survival 6.8 years. 35% had a family history suggestive of dementia. In patients with FTD the clinical expression was a combination of behavioral and personality disorders together with language impairment. Magnetic resonance imaging showed frontal and/or temporal atrophy in 62% of cases and SPECT showed frontal and/or temporal hypoperfusion in 75%. The P301L tau mutation was detected in four patients (two of them siblings) and the A303AfsX57 progranulin mutation in one. Necropsy was performed in five patients, revealing FTLD with ubiquitininmunoreactive inclusions (FTLD-U) and motor neuron disease in two cases, FTLD-U with <<cat's-eye>> shaped intranuclear inclusions in the case with the progranulin mutation and FTLD tauopathy with predominance of 4R tau in the remaining two, both with the P301L mutation. Our results are similar to those of the great European series. FTLD must be suspected in presenile patients with prominent behavioral and/or language disorders. Neuroimaging supports the diagnosis in the majority of cases. The huge sociofamiliar impact of FTLD, presenile onset, high frequency of familial history of dementia and possibility of genetic study and counseling highlight its clinical relevance. | 18,802,798 |
Healing diabetic foot ulcers using cortical bone fenestration and cell therapy. | Chronic wounds with exposed bone present a challenge for clinicians. Without intact periosteum, cortical bone is relatively avascular and provides a poor base for wound healing and skin grafting. It has been shown that cortical bone fenestration and decortication can expedite wound healing in exposed calvarial bone. We present a case study where cortical bone fenestration and the subsequent application of human skin equivalent were used to heal a chronic wound of the lower extremity. We propose that this technique can facilitate the production of granulation tissue, and can aid the healing of chronic wounds of the lower extremities associated with exposed bone. | 18,802,886 |
Creative limb-salvage surgical and endovascular revascularization strategies in treating critical limb ischemia. | Critical limb ischemia (CLI) is implicated in cases of between 220,000 to 240,000 amputations in the United States and Europe annually. Over the last five years, great technical strides have been made in both the surgical and nonsurgical endovascular treatments of CLI. This chapter analyzes and highlights those creative limb salvage strategies now used to treat CLI and save limbs. | 18,802,888 |
A long-survived case with solitary splenic metastasis from ovarian carcinoma. | A61-year-old postmenopausal woman with ovarian carcinoma was treated with two surgical operations and a series of platinum-based chemotherapy. A solitary metastasis into the splenic parenchyma was identified 33 months after the second surgery by abdominal computed tomography with an increased serum level of CA-125. She underwent a pancreaticosplenectomy and received platinum-based adjuvant chemotherapy continuously for 2 years. Her serum CA-125 level decreased to a normal range and she has lived without any recurrence for more than 10 years after the splenectomy. Solitary metastases from ovarian cancer into the splenic parenchyma are extremely rare. Among 18 cases previously reported, this present case shows the longest disease-free survival. Because these cases show favorable prognosis after splenectomy, surgical treatment should be considered along with adjuvant chemotherapy. | 18,802,901 |
Evaluation of the accuracy of three CT-free surgical navigation systems in total knee arthroplasty (TKA) using a coordinate measuring machine. | Previous studies have shown that the accuracy of computer-assisted surgery (CAS) via computed tomography (CT) free systems is useful when applied in the clinical realm. However, few studies have compared CAS systems to the current gold standard, manually applied measuring guides. Thirty total knee arthroplasties (TKA) were performed on artificial Sawbones knees using three different navigational systems. The TKAs were performed by a fellowship-trained joint reconstruction surgeon as well as a third- and a fourth-year orthopedic resident to assess differences in performance with regard to surgical experience. Using a two-way multivariate analysis of variance (MANOVA), no statistical differences were found in the accuracy of each of the three CAS navigational systems. Similarly, no differences were found between the accuracy of CAS systems and the gold standard measuring method. No differences in performance were found between the orthopedic residents and the fellowship-trained surgeon, suggesting a relatively small learning curve and usability. Definitive assessment of the clinical efficacy should be further assessed in a cadaveric study or, ideally, by way of a randomized clinical trial. | 18,802,908 |
Restoration of function in complete spinal cord injury using peripheral nerve rerouting: a summary of procedures. | Until relatively recently, few procedures have been developed that restore significant motor and sensory function in individuals with obsolete (ie, chronic), complete spinal cord injury (SCI). Building upon the methodology used to treat brachial root avulsion, the authors have developed peripheral nerve-rerouting procedures that have restored some function in hundreds of patients with such SCI. Many of the treated patients have regained life-enhancing function depending upon their injury level, such as walking with assistive devices, partial hand function, urination, sexual sensation, etc. Although sophisticated surgeries, the basic concept is theoretically simple: a functional nerve from above the injury site is rerouted and connected to a paralysis-affected peripheral nerve below the injury site. This Chapter summarizes more than a dozen rerouting procedures, which restore function that range from breathing to toe sensation. This summary discusses the indications and criteria for choosing the best donor nerve based on the specific injury level, and emphasizes major procedural features such as the use of selected interfascicular anastomosis, modified end-to-side suture techniques, vascularized donor nerves, a muscle trigger for the synchronized contraction of congenerous muscles, and reconstruction procedures to restore donor-nerve function. | 18,802,915 |
Focus on HTR2C: A possible suggestion for genetic studies of complex disorders. | HTR2C is one of the most relevant and investigated serotonin receptors. Its role in important brain structures such as the midbrain, the lateral septal complex, the hypothalamus, the olfactory bulb, the pons, the choroid plexus, the nucleus pallidus, the striatum and the amygdala, the nucleus accumbens and the anterior cingulated gyrus candidate it as a promising target for genetic association studies. The biological relevance of these brain structures is reviewed by way of the focus on HTR2C activity, with a special attention paid to psychiatric disorders. Evidence from the genetic association studies that dealt with HTR2C is reviewed and discussed alongside the findings derived from the neuronatmic investigations. The reasons for the discrepancies between these two sets of reports are discussed. As a result, HTR2C is shown to play a pivotal role in many different psychiatric behaviors or psychiatric related disrupted molecular balances, nevertheless, genetic association studies brought inconsistent results so far. The most replicated association involve the feeding behavior and antipsychotic induced side effects, both weight gain and motor related: Cys23Ser (rs6318) and -759C/T (rs3813929) report the most consistent results. The lack of association found in other independent studies dampens the clinical impact of these reports. Here, we report a possible explanation for discrepant findings that is poorly or not at all usually considered, that is that HTR2C may exert different or even opposite activities in the brain depending on the structure analyzed and that mRNA editing activity may compensate possible genetically controlled functional effects. The incomplete coverage of the HTR2C variants is proposed as the best cost-benefit ratio bias to fix. The evidence of brain area specific HTR2C mRNA editing opens a debate about how the brain can differently modulate stress events, and process antidepressant treatments, in different brain areas. The mRNA editing activity on HTR2C may play a major role for the negative association results. | 18,802,918 |
Identification of a novel mutation in DKC1 in dyskeratosis congenita. | Dyskeratosis congenita (DC) is a rare congenital syndrome characterized by the triad of reticular skin pigmentation, nail dystrophy and mucosal leukoplakia, and the predisposition to bone marrow failure and malignancy. DC is genetically heterogeneous and X-linked and autosomal forms of the disease exist. Here, we report the clinical description and mutation analysis of a Russian family with X-linked DC. A novel mutation in DKC1 raised de novo in the maternal grandmother's gamete was found; this mutation is a 2 bp inversion in exon 3: NM_001363:c.166_167invCT (Leu56Ser). | 18,802,941 |
Behavioral and nutritional factors and geohelminth infection among two ethnic groups in the Terai region, Nepal. | Geohelminthiasis is a major health problem in many developing countries. This study was designed to evaluate the role of behaviors and the nutritional status of people with geohelminth infection in two indigenous ethnic groups in lowland Terai, Nepal. One hundred and fourteen individuals (55 Mushar and 59 Tharu) aged 20-60 years participated, and a structured questionnaire was used to investigate socioeconomic status and behaviors. Nutritional status was assessed by anthropometric measurements. Ninety five stool samples of the participants were collected for parasitological analysis. The results showed that the prevalence of geohelminthiasis was 42.1%: 26.3% of the subjects were infected with roundworm, 9.5% with hookworms, and 6.3% with whipworm. Multivariate logistic regression analysis revealed that "not using soap for hand-washing" (adjusted OR = 5.27; 95% CI: 1.41-19.78) and height (adjusted OR = 0.88, 95% CI: 0.79-0.99) were associated with the prevalence of roundworm. "Walking barefoot when outdoor" was associated with the prevalence of hookworm (chi-square test, P = 0.01). Ethnicity was not associated with the prevalence of either of the geohelminths. Because unhygienic behaviors and chronic malnutrition were closely associated with the people's recognition and subsistence pattern, elimination of geohelminth infection in Terai would be possible if deworming campaigns were implemented with in-depth health education and modern agricultural technology. | 18,802,944 |
Clinical characteristics and outcome of children with Burkitt lymphoma in Uganda according to HIV infection. | Characteristics of children with Burkitt lymphoma (BL) and HIV infection have not been described in Uganda before. We reviewed records at Uganda Cancer Institute (UCI) for years 1994-2004, to compare clinical features and outcome of BL in children who are HIV positive and negative (HIV+, HIV-). As statistical methods we used Student's t-test, Chi-square and Kaplan-Meier's to compare both groups. Of 1,462 records of children retrieved, 228 met the eligibility criteria and were reviewed (158 HIV-, 70 HIV+). There were 139 (61%) males and 89 (39%) females. The mean age was 6.9 years (HIV+ 6.7, HIV- 7.1). One hundred seventy-one cases (75%) had facial tumor (HIV+ 71.4%, HIV- 76.6%). HIV positive children presented significantly with extrafacial disease (lymphadenopathy 67%, hepatic masses 51%, and thoracic masses 10%). Presentation with advanced stage disease occurred more frequently in HIV positive patients compared to HIV negative patients. Treatment response rates to chemotherapy were similar irrespective of HIV status. However, overall survival was poorer in HIV positive patients with a median survival of 11.79 months (P-value < 0.000, 95% CI 8.65-14.92). BL in Uganda presents frequently with facial disease irrespective of HIV status. However HIV+ BL also presents commonly with extra facial sites, mainly lymphadenopathy. There is no difference in response to treatment with chemotherapy, but HIV+ BL patients have poorer survival. There is need for further characterization of BL in Uganda to understand the role of HIV in disease process and outcome. | 18,802,952 |
Phenotypic analyses of a medaka mutant reveal the importance of bilaterally synchronized expression of isthmic fgf8 for bilaterally symmetric formation of the optic tectum. | Developing neural tubes are bilaterally symmetric in all vertebrate embryos, irrespective of the presence of gene networks that generate left-right asymmetry. To explore the mechanisms that underlie the bilaterally symmetric formation of the neural tube, we examined a medaka (Oryzias latipes) dominant mutant, Oot, the neural tube of which transiently lacks normal symmetry in the optic tectum. We found that spatial changes in isthmic fgf8 expression do not occur on one side of the mutant, resulting in a transient desynchronized expression that correlates with tectal asymmetry. The application of exogenous FGF8 on one side of a wild-type embryo mimics the Oot phenotype, indicating that the bilaterally equivalent expression of isthmic fgf8 is crucial for the bilaterally symmetric development of the tectum. These results suggest that tectal symmetry is not a "default" state, but rather is maintained actively by a bilaterally coupled and synchronized regulation of isthmic fgf8 expression. | 18,802,954 |
DFT calculations as a powerful technique to probe the crystal structure of Al(acac)3. | (27)Al, (17)O and (13)C chemical shieldings of aluminum acetylacetonate complex, Al(acac)(3), were calculated at some Density Functional Theory (DFT) levels of theory. In these calculations the X-ray structures of its different polymorphs were used. Using these calculated data observed discrepancies between the X-ray crystallography and solid state NMR experiment were explained in terms of the quality of the NMR data. In this survey we resorted to the simulated spectra using our calculated chemical shifts. In order to confirm our conclusions, electric field gradient (EFG) tensors of the (27)Al and (17)O nuclei were calculated at the same levels of theory as used in the chemical shielding calculations. On the other hand, these calculated chemical shifts and nuclear quadrupole coupling constants (NQCCs) made a correlation between X-ray crystallography and solid state NMR experiments. | 18,802,968 |
[Role of duodenum in regulation of plasma ghrelin level and body mass index after subtotal gastrectomy]. | To investigate the role of duodenum in regulation of ghrelin and body mass index (BMI) and the correlation between ghrelin and BMI after subtotal gastrectomy. Forty-two patients with T(0-1)N(0-1)M(0) gastric cancer were divided into two groups after gastrectomy according to digestive reconstruction pattern, Billroth I group (n=23) and Billroth II group (n=19) respectively. Plasma ghrelin levels were determined by radioimmunoassay (RIA) before and at day 1, 7, 30 and 360 after gastrectomy,and BMIs were also measured. Two groups had identical postoperative trends in ghrelin alterations during the early stage, both dropping to nadir at day 1 (36.7% vs 35.7%), then markedly increasing at day 7 (51.0% vs 51.1%). At day 30, ghrelin level of Billroth I group was slightly higher than that of Billroth II group. At day 360, ghrelin level of Billroth I group recovered to 93.6%, approaching though lower than preoperative level and no significant difference was displayed, while ghrelin level of Billroth II group recovered only to 81.6% of preoperational level and significant difference existed (P=0.033). Compared with preoperative levels, ghrelin of two groups decreased by 6.9% and 18.4% while BMI by 3.3% and 6.4% respectively, liner regression correlations were revealed in both groups between decrease magnitudes(R(1)(2)=0.297,P=0.00;R(2)(2)=0.559,P<0.001). Anatomico-physiological duodenum compensatively promotes ghrelin recovery, accordingly enhances BMI after gastrectomy. Regarding patients with insufficient ghrelin secretion, ghrelin is positively correlated with BMI. | 18,803,044 |
[Effects of phosphatase of regenerating liver cell-3 gene silence by RNA interference on the expression of matrix metalloproteinases-2,-9 in human colon cancer cells]. | To explore the effects and associated mechanism of phosphatase of regenerating liver cell-3 (PRL-3) on the invasion of human colon cancer cell. After colon cancer cell line HCT116 was transfected with PRL-3 small interfering RNA (siRNA), the mRNA and protein expression of PRL-3 and matrix metalloproteinase 2 (MMP-2) and MMP-9 were determined by real time RT-PCR and Western blot respectively. The anchorage-independent growth was examined using clone formation assay in soft agar, and invasion ability was evaluated by boyden chamber model. Then the transfected HCT116 cells were implanted into nude mice and the tumor growth was observed. PRL-3 siRNA could inhibit anchorage-independent growth of HCT116 cells in a dose-dependent manner in vitro. The mRNA and protein expression of MMP-2 and MMP-9 were down-regulated by PRL-3 siRNA. HCT116 cells invaded striated muscle and vessels in control nude mice but such phenomena were not found in transfected HCT116-implanted nude mice in vivo. PRL-3 siRNA inhibit the invasion of colon cancer cells possibly through the down-regulation of MMP-2 and MMP-9. | 18,803,055 |
Risk factors and mechanisms of anaphylactoid reactions to acetylcysteine in acetaminophen overdose. | Adverse effects to N-acetylcysteine (NAC) are well recognized, but their etiology and incidence are unclear. The nature and severity of adverse effects were prospectively studied in 169 patients and potential reaction mediators studied in 22 patients. Adverse effects were minimal in 101 (59.8%), moderate in 51 (30.2%), and severe in 17 (10.1%). Features were nausea (70.4%), vomiting (60.4%), flushing (24.9%), pruritus (20.1%), dyspnea (13.6%), chest pain (7.1%), dizziness (7.7%), fever (4.7%), wheeze and bronchospasm (7.1%), and rash and urticaria (3.6%). Serum acetaminophen concentration was lower in patients with severe adverse effects: median (IQR) 46 mg/L (0 to 101 mg/L), moderate 108 mg/L (54 to 178 mg/L), and minimal 119 mg/L (77 to 174 mg/L), p = 0.002. Family history of allergy and female gender were independent risk factors for adverse effects. Severity of adverse effects was associated with histamine release: AUC for change from baseline histamine was -6 ng/mL min (-60 to 11 ng/mL min) in the minimal group, 26 ng/mL min (3-129 ng/mL min) in the moderate group, and 49 ng/mL min (21-68 ng/mL min) in the severe group (p = 0.01). There was no increase in tryptase and no differences between groups for NAC concentrations or hemostatic and inflammatory variables (factors II, VII, IX, X, vWF, tPA, IL6, and CRP). Severity of adverse effects correlates with the extent of histamine release. Histamine release appears independent of tryptase suggesting a non-mast cell source. Acetaminophen is protective against adverse effects of NAC, and mechanisms by which acetaminophen might lessen histamine release require further attention. | 18,803,085 |
Evaluation of the patterns of potentially toxic exposures in Mississippi following Hurricane Katrina. | To describe the changes in the frequency of selected toxic exposures reported to the state poison control center following Hurricane Katrina. The numbers of selected exposures reported to the Mississippi Poison Control Center at 0-2 weeks, 3-4 weeks, and 5-12 weeks following Hurricane Katrina were compared to those for the same time periods in the previous 3 years. Absolute numbers of exposures and odds ratios with confidence intervals were used for comparison. In the first 2 weeks following Hurricane Katrina, there were 44 reported gasoline exposures compared to 7 expected, 8 lamp oil exposures compared to 1 expected, and seven carbon monoxide exposures compared to 1 expected. Only gasoline exposures remained elevated in the second 2 weeks period following the hurricane. Lamp oil exposures were elevated during the 5-12 week recovery period. There was no increase in the frequency of exposures to household cleaning agents, food poisoning, pediatric exposures, drug-related suicide events, bites and stings, or venomous snakebites. The most common toxic exposures following Hurricane Katrina were related to the lack of typical energy sources, electricity, and gasoline. | 18,803,086 |
Energy cost and mechanical efficiency of riding a human-powered recumbent bicycle. | When dealing with human-powered vehicles, it is important to quantify the capability of converting metabolic energy in useful mechanical work by measuring mechanical efficiency. In this study, net mechanical efficiency (eta) of riding a recumbent bicycle on flat terrain and at constant speeds (v, 5.1-10.0 m/s) was calculated dividing mechanical work (w, J/m) by the corresponding energy cost (C(c), J/m). w and C(c) increased linearly with the speed squared: w = 9.41 + 0.156 . v(2); C(c) = 39.40 + 0.563 . v(2). eta was equal to 0.257 +/- 0.0245, i.e. identical to that of concentric muscular contraction. Hence, i) eta seems unaffected by the biomechanical arrangement of the human-vehicle system; ii) the efficiency of transmission seems to be close to 100%, suggesting that the particular biomechanical arrangement does not impair the transformation of metabolic energy in mechanical work. When dealing with human-powered vehicles, it is important to quantify mechanical efficiency (eta) of locomotion. eta of riding a recumbent bicycle was calculated dividing the mechanical work to the corresponding energy cost of locomotion; it was practically identical to that of concentric muscular contraction (0.257 +/- 0.0245), suggesting that the power transmission from muscles to pedals is unaffected by the biomechanical arrangement of the vehicle. | 18,803,095 |
Wrist strength is dependent on simultaneous power grip intensity. | The effect of grip activities on wrist flexion/extension strength was examined. Twelve healthy subjects performed maximum wrist flexion/extension exertions with one of five levels of simultaneous grip effort: minimum effort; preferred effort; 30%, 60% and 100% maximum voluntary contraction. As grip force increased from the minimum to the maximum effort, average wrist flexion strength increased 34% and average wrist extension strength decreased 10%. It appears that the finger flexor tendons on the volar aspect of the wrist act agonistically in wrist flexion and act antagonistically to wrist extension. When an object gripped by the hand is fragile or uncomfortable, the reduced finger flexor activity will limit wrist flexion strength. Gripping a slippery object that requires high grip effort will result in reduced wrist extension strength. Grip force should be controlled during measurement of wrist flexion or extension strength. When analysing a task that involves both grip and wrist exertions, use of grip/wrist strength values that were measured during grip exertions only, or wrist exertions only, may incorrectly estimate the true grip/wrist strength, as grip and wrist activities significantly interact with each other as demonstrated in this paper. | 18,803,097 |
Pharmacologic treatment of disturbed sleep in the elderly. | Disturbed sleep is common in the elderly, who, as a group, take a disproportionately large number of hypnotic medications. Benzodiazepine hypnotics, as well as the newer benzodiazepine receptor agonists, are the primary treatments for these late-life sleep disorders and are effective and safe when used within recommended prescribing guidelines. The elderly also receive other psychiatric medications to induce sleep, although these are off-label uses not well supported by research literature. There is also no literature support for the use of over-the-counter sleep preparations, although both melatonin and a melatonin receptor agonist appear to be moderately effective and safe. Prescribing guidelines for the elderly continue to emphasize short-term, low-dose use, with short-half-life medications. Hypnotic drugs should be used in conjunction with nonmedication treatments, including appropriate sleep hygiene practice, and treatment of other medical or psychiatric causes of disturbed sleep. | 18,803,102 |
Impact of repeated pesticide applications on the binding and release of methyl 14C-monocrotophos and U-ring labelled 14C-carbaryl to soil matrices under field conditions. | The dissipation of (O-methyl-14C) monocrotophos and U-ring labelled 14C-carbaryl was monitored for over two years in absence and presence of other insecticides using in situ soil columns. The dissipation of 14C-monocrotophos from soil treated with methomyl and carbaryl showed a faster rate of downward movement than in a control column tagged with the labelled insecticide alone. The same trend was observed in experiments with 14C-carbaryl that dissipated more readily in soil treated with non-labelled monocrotophos and methomyl. In the presence of other insecticides the percentage of bound residues was generally lower than in control experiments. The bound residues at the top of the column are released at a low rate under conditions prevailing in the field. The overall time required for dissipation of 50% of monocrotophos and carbaryl (t50) as estimated from control experiment was approximately 20 and 24 weeks, respectively. The data indicate that repeated applications of pesticides might enhance the release of 14C-bound residues. | 18,803,114 |
Obtundation and seizure following ondansetron overdose in an infant. | Ondansetron, an increasingly prescribed 5-HT(3) antagonist used in the management of nausea and vomiting of various etiologies, has a well-established safety profile in therapeutic use. However, little is known about its effects in the setting of an overdose. We describe the first case of severe toxicity in an infant who unintentionally ingested a large quantity of ondansetron. A 12-month-old infant who ingested seven to eight tablets of his mother's Zofran (ondansetron) ODT 8 mg rapidly developed obtundation and myoclonic movements. While treated by health care providers, he developed seizures, hepatotoxicity, QTc prolongation, and a serotonin syndrome that required endotracheal intubation and intensive care unit management. His clinical status improved over the course of 24 h with supportive care, and he was discharged to home with no sequelae. With the increasing popularity of ondansetron among health care providers, particularly for the control of nausea in pregnant women, toddlers in the household may become inadvertently exposed to ondansetron toxicity. This case portrays that, despite the safety of this agent in therapeutic dosage, severe toxicity may be seen in excessive amounts, particularly in infants. Health care providers should recognize the risk for acute toxicity following ondansetron overdose, particularly in infants and toddlers. | 18,803,119 |
[Agreement among ophthalmologists and primary care physicians in the evaluation of retinographies of diabetic patients]. | To assess the extent of agreement in the evaluation of non-mydriatic retinographies of diabetic patients among ophthalmologists and a group of primary care physicians with previous training. The study was divided in two phases. In the first phase, the four participants were instructed in the interpretation of retinographies. The second phase involved the evaluation of 1000 images of 200 patients, 100 without retinopathy and 100 with signs of diabetic retinopathy. The four participants had to decide if the images did or did not show evidence of diabetic retinopathy. Kappa index was used to assess the extent of agreement. A percentage disagreement of 15% with a precision of 5% (+/-5%) with a confidence level of 95% was considered adequate. The percentage of coincident diagnoses among ophthalmologists and primary care physicians was between 89 and 97.5%. With respect to the assessment of the agreement, the kappa index was between 80 and 95%. In all cases the confidence interval was at least 85%. After an adequate training process, the reliability of evaluation of non-mydriatic retinographies of diabetic patients by primary care physicians was very high. This could allow the establishment of screening for diabetic retinopathy at the primary care level. Advantages of this system include a greater involvement of primary care physicians in the global management of diabetic patients and a lower demand for ophthalmic attention. | 18,803,124 |
[The social and familial dimension: experiences of caregivers and people with multiple sclerosis. The GEDMA study]. | Comparing the perceptions of multiple sclerosis (MS) patients and caregivers with regard to the same social and familial issues, as well as delving deeper into the factors that determine the quality of life of these patients and their relatives by using a qualitative methodology, can help us to complete the information on the same topic that has already been collected using scales and quantitative protocols. To analyse how a group of people with MS and their caregivers perceive the disease by examining the way they talk about their experience with it. A qualitative methodology was used; more particularly, data were obtained by holding six discussion groups made up of patients and caregivers, who were members of MS patient associations. People with MS reported the social stigma attached to suffering from the disease. Many of the caregivers thought that patients with MS did not accept the disease and felt that over-protection was of little help in coming to terms with the disease and should therefore be avoided. Remunerated work was described by caregivers as a factor that, at the same time, generated and protected the burden. The social stigma, the lack of work and coming to terms with MS were the greatest issues for the patient, while support from the family network, the relationship that should be established with the patient, the impact of MS on children and the role played by remunerated work were the main dimensions of the disease for the caregiver. | 18,803,152 |
[Anatomical and neurochemical bases accounting for the frequent association between headaches and sleep: the hypnic headache paradigm]. | The relationship between headache and sleep is complex and runs in two directions. Headache may be the consequence of a (primary or secondary) sleep disorder or its cause (in chronic tension-type headache and/or chronic migraine with or without painkiller abuse). It can also be related to sleep in an intrinsic way, as in the case of hypnic headache (which only appears during sleep) or other primary headaches, such as migraine and certain trigeminal-autonomic cephalgias (which can appear during the waking state or during sleep); this type of headache occurs mostly during REM sleep. The neural pathways that control sleep and pain are anatomically, physiologically and neurochemically cross-linked. These neural systems are located in the brain stem, the hypothalamus and the basal brain. Such cross-links are produced on two different levels. On the one hand, they occur in the serotoninergic nuclei of the brain stem, whose activity in physiologically diminished during REM sleep and which are involved in antinociceptive control. On the other hand, they are also to be found in the hypothalamus, where serotoninergic terminals have been detected in the suprachiasmatic nucleus (SCN). As cells in the SCN are lost with age, their circadian and homeostatic functioning fails, the activity of the hypothalamus-pineal axis is reduced and the endogenous melatonin rhythm is altered. This results in a disorder affecting the control of the sleep-waking cycle and antinociceptive control. Dysfunctions in these neuronal networks in the brain stem (especially in the serotoninergic nuclei) or the hypothalamus (SCN) can account for headaches that begin in the REM phase of sleep and affect biologically predisposed subjects. | 18,803,160 |
A method for rapidly predicting drug tissue distribution using surfactant vesicle electrokinetic chromatography. | Lung tissue distribution of an inhaled drug is important for its potency in the airways and with minimum systemic effects within its dose range. As the lung has the smallest diffusion distance of all the organs in the body and negligible diffusion delays, the characteristics of drug distribution in the lung will mainly depend on drug binding to both tissue and plasma protein. This research aims to develop and evaluate surfactant vesicle electrokinetic chromatography (SEKC) methods for high throughput profile prediction of tissue distribution for inhaled drugs. Several electrokinetic chromatography methods reported in the literature, as well as immobilised artificial membrane chromatography, were compared and evaluated in respect to chromatographic characteristics and statistical correlations. Among these methods, the docusate sodium salt (AOT) SEKC system showed good reproducibility, short run time, and the highest selectivity for alkylphenone test compounds. It also showed a significant statistical correlation between the retention of inhaled drugs and their in vivo volume of distribution at steady-state (V(ss)) in whole human body neglecting the plasma protein-binding differences. Stronger correlations were observed between the AOT SEKC retention of a series of basic drugs and their rat lung tissue-to-plasma water partitioning coefficient (K(pu)), which is affected only by drug binding to the tissue constituent. Further, on comparing correlations between AOT SEKC retention and K(pu) at various rat tissues, it was observed that the strongest correlation was with lung tissue distribution, while the weakest was with brain tissue distribution. | 18,803,182 |
Ruthenium complexes of substituted hydrazine: new solution- and solid-state binding modes. | The methylhydrazine complex [Ru(NH(2)NHMe)(PyP)(2)]Cl(BPh(4)) (PyP=1-[2-(diphenylphosphino)ethyl]pyrazole) was synthesised by addition of methylhydrazine to the bimetallic complex [Ru(mu-Cl)(PyP)(2)](2)(BPh(4))(2). The methylhydrazine ligand of the ruthenium complex has two different binding modes: side-on (eta(2)-) when the complex is in the solid state and end-on (eta(1)-) when the complex is in solution. The solid-state structure of [Ru(PyP)(2)(NH(2)NHMe)]Cl(BPh(4)) was determined by X-ray crystallography. 2D NMR spectroscopic experiments with (15)N at natural abundance confirmed that in solution the methylhydrazine is bound to the metal centre by only the -NH(2) group and the ruthenium complex retains an octahedral conformation. Hydrazine complexes [RuCl(PyP)(2)(eta(1)-NH(2)NRR')]OSO(2)CF(3) (in which R=H, R'=Ph, R=R'=Me and NRR'=NC(5)H(10)) were formed in situ by the addition of phenylhydrazine, 1,1-dimethylhydrazine and N-aminopiperidine, respectively, to a solution of the bimetallic complex [Ru(mu-Cl)(PyP)(2)](2)(OSO(2)CF(3))(2) in dichloromethane. These substituted hydrazine complexes of ruthenium were shown to exist in an equilibrium mixture with the bimetallic starting material. | 18,803,189 |
Theoretical study of the human bradykinin-bradykinin B2 receptor complex. | The interaction of bradykinin (BK) with the bradykinin B2 receptor (B2R) was analyzed by using molecular modeling (MM) and molecular dynamics (MD) simulations. A homology model for B2R has been generated and the recently determined receptor-bound solid-state NMR spectroscopic structure of BK (Lopez et al., Angew. Chem. 2008, 120, 1692-1695; Angew. Chem. Int. Ed. 2008, 47, 1668-1671) has been modeled into the binding pocket of the receptor to probe the putative ligand-receptor interface. The experimental hormone structure fitted well into the binding pocket of the receptor model and remained stable during the MD simulation. We propose a parallel orientation of the side chains for Arg1 and Arg9 in BK that is bound to B2R. The MD simulation study also allows the conformational changes that lead to the activated form of B2R to be analyzed. The hydrogen bond between N140 (3.35) and W283 (6.48) is the key interaction that keeps the receptor in its inactive form. This hydrogen bond is broken during the MD simulation due to rotation of transmembrane helix 3 (TM3) and is replaced by a new hydrogen bond between W283 (6.48) and N324 (7.45). We propose that this interaction is specific for the activated form of the bradykinin B2 receptor. Additionally, we compared and discussed our putative model in the context of the structural model of the partially activated rhodopsin (Rh*) and with the known biochemical and structural data. | 18,803,210 |
Cyclodextrin-based nonaqueous electrokinetic chromatography with UV and mass spectrometric detection: application to the impurity profiling of amiodarone. | The potential of nonaqueous electrokinetic chromatography (NAEKC) using cyclodextrins (CD) for the analysis of basic drugs and related compounds was evaluated. Both UV absorbance and mass spectrometric (MS) detection were employed. Addition of neutral CD to the NA background electrolyte did not significantly enhance the separation of a test mixture of basic drugs, and no change in selectivity was observed. In contrast, anionic single-isomer-sulfated CD strongly added to the selectivity of the NAEKC system inducing an improved resolution among the test compounds and increasing the migration time window. The applicability of the NAEKC system using anionic CD is demonstrated by the profiling of a sample of the drug amiodarone that had been stored for 1 year at room temperature. Amiodarone is poorly soluble in water. NAEKC-UV analysis indicated the presence of at least seven impurities in the amiodarone sample. In order to identify these compounds, the NAEKC system was coupled directly to electrospray ionization (ESI) ion-trap MS. The total of detected impurities increased to 12 due to the added sensitivity and selectivity of MS detection. Based on the acquired MS/MS data, three sample constituents could be identified as 'known' impurities (British Pharmacopoeia), whereas for three unknown impurities molecular structures could be proposed. Estimated limits of detection for amiodarone using the NAEKC method were 1 microg/mL with UV detection and 15 ng/mL with ESI-MS detection (full-scan). Based on relative responses, the impurity content of the stored drug substance was estimated to be 0.33 and 0.47% using NAEKC-UV and NAEKC-ESI-MS, respectively. | 18,803,218 |
Electrophoresis studies on the contaminating glycosaminoglycans in commercially available hyaluronic acid products. | Hyaluronic acid (HA) samples showing inhibition effect on digestion with testicular hyaluronidase (HAase) were found from 16 commercially available HA products, which were supplied from 11 different manufacturers. Most of these HA samples (six samples) were derived from the rooster comb, and one sample was derived from the human umbilical cord. HA oligosaccharides produced by exhaustive digestion of these HA samples with testicular HAases were monitored by capillary electrophoresis, and we found that a few HA samples gave no oligosaccharide products. Detailed analysis of HA samples by cellulose acetate membrane electrophoresis revealed that the HA samples were not digested with HAase because of the presence of a small amount of dermatan sulfate (DS). Analysis of disaccharide units of these HA samples produced by digestion with chondroitinase ABC supported the observations. And the content of DS in the sample was estimated to be ca. 8%. In contrast, these HA samples were easily digested with bacterial hyaluronate lyases from Streptomyces hyalurolyticus and Streptococcus dysgalactiae and gave endproducts of unsaturated disaccharide or unsaturated tetra- or hexasaccharides. The results suggested that the inhibitory effect of DS on HAase is specific to endo-type hydrolase (i.e. testicular HAase). In addition, pharmaceutical preparations of HA derived from rooster comb were easily digested with testicular HAase. These findings will be useful information for clinical or cosmetic use of HA preparations in terms of their half-life. | 18,803,225 |
In vitro differentiation of human calvarial suture derived cells with and without dexamethasone does not induce in vivo-like expression. | Osteogenic supplements are a requirement for osteoblastic cell differentiation during in vitro culture of human calvarial suture-derived cell populations. We investigated the ability of ascorbic acid and beta-glycerophosphate with and without the addition of dexamethasone to stimulate in vivo-like osteoblastic differentiation. Cells were isolated from unfused and prematurely fused suture tissue from patients with syndromic and non-syndromic craniosynostosis and cultured in each osteogenic medium for varying lengths of time. The effect of media supplementation was investigated with respect to the ability of cells to form mineralised bone nodules and the expression of five osteodifferentiation marker genes (COL1A1, ALP, BSP, OC and RUNX2), and five genes that are differentially expressed during human premature suture fusion (GPC3, RBP4, C1QTNF3, WIF1 and FGF2). Cells from unfused sutures responded more slowly to osteogenic media but formed comparable bone nodules to fused suture-derived cells after 16 days of culture in either osteogenic media. However, gene expression differed between unfused and fused suture-derived cells, as did expression in each osteogenic medium. When compared to expression in the explant tissue of origin, neither medium induced a level or profile of gene expression similar to that seen in vivo. Overall, our results demonstrate that cells from the same suture that are isolated during different stages of morphogenesis in vivo, despite being de-differentiated to a similar level in vitro, respond uniquely and differently to each osteogenic medium. Further, we suggest that neither cell culture medium recapitulates differentiation via activation of the same genetic cascades as occurs in vivo. | 18,803,234 |
Wnt/Frizzled family members mediate olfactory sensory neuron axon extension. | A comprehensive model has yet to emerge, but it seems likely that numerous mechanisms contribute to the specificity of olfactory sensory neuron (OSN) axon innervation of the olfactory bulb. Elsewhere in the nervous system the Wnt/Fz family has been implicated in patterning of anterior-posterior axes, cell type specification, cell proliferation, and axon guidance. Because of our work describing cadherin-catenin family member expression in the primary olfactory pathway, and because mechanisms of Wnt-Fz interactions can depend in part on catenins, we were encouraged to explore Wnt-Fz expression and function in OSN axon extension. Here, we show that OSNs express Fz-1, Fz-3, and Wnt-5a, whereas olfactory ensheathing cells (OECs) express Wnt-4. Fz-7 is also expressed in the olfactory nerve by cells that delineate large axon fascicles, but are negative for OEC markers. Fz-1 showed a developmental downregulation. However, in adults it is expressed at different levels across the olfactory epithelium and in restricted glomeruli across the olfactory bulb, suggesting an important role in the formation and maintenance of OSN connections to the olfactory bulb. Reporter TOPGAL mice demonstrated that some OECs located in the inner olfactory nerve layer can respond to Wnt ligands. Of further interest, we show here with in vitro assays that Wnt-5a increases OSN axon outgrowth and alters growth cone morphology. Our data point to a key role for Wnt/Fz molecules in the development of the mouse olfactory system, providing complementary mechanisms required for OSN axon extension and coalescence. | 18,803,244 |
Normal blood cells reference intervals of healthy adults at the Gaza Strip-Palestine. | Hematological parameters are affected by different factors that include age, sex, smoking, ethnicity, and environmental altitude. It has been justified that each population must establish its own normal reference intervals to be used in clinical assessments and interpretations. Hematological reference intervals for adults from the Gaza Strip-Palestine have never been addressed. Therefore, this study was designed and aimed at the establishment of normal blood cells reference intervals for healthy adults at the Gaza Strip-Palestine. This study involved 89,491 apparently healthy individuals (from both sexes and from the different governorates of the Gaza Strip) who were referred to the Thalassemia Central Laboratory during the period from September 2000 until February 2008. Complete blood counts were performed. Subjects were categorized into subgroups according to gender, smoking habit, and age (15-18, 19-45, and >45 years old). For each subgroup, descriptive and comparative statistical analysis was performed for hematological parameters. The results showed substantial differences between males and females, between smokers and nonsmokers, and between the different age groups. Moreover, reference intervals derived from our population are markedly shifted downward as compared with Western European and American populations. It was concluded that separate and region-specific reference intervals based on gender, smoking, and age for the Palestinian population at the Gaza Strip should be generalized for clinical laboratories and clinical practitioners, which could help in interpreting laboratory hematological tests more specifically, and potentially develop the quality of medical care provided to patients. | 18,803,270 |
Comparative evaluation of FASTPlaque assay with PCR and other conventional in vitro diagnostic methods for the early detection of pulmonary tuberculosis. | Rapid and accurate diagnosis of symptomatic patients of pulmonary tuberculosis (TB) is highly desirable to minimize the spread of the disease in the society. We, therefore, compared the usefulness of various conventional diagnostic methods, the in-house polymerase chain reaction (PCR), and the FASTPlaque assay in this study. Laboratory data of 150 patients with clinical diagnosis of pulmonary TB and 50 controls were included in this study. The sputa from all these 200 individuals were subjected to acid-fast staining, culture on Lowenstein-Jensen (L-J) slants, automated BACTEC-MGIT-960 culture methods, and a mycobacteriophage assay. A mycobacterium genus and Mycobacterium tuberculosis species-specific PCRs were also done and samples positive on both PCRs were considered as standard for comparison. Of the 5 in vitro diagnostic tests, PCR method was found to be the most rapid, sensitive, and specific, detecting all the 150 cases of pulmonary TB without any false-positive and negative result. In comparison with PCR the sensitivity of MGIT-960 was 90%, followed by FASTPlaque assay (76.7%), L-J culture method (73.3%), and microscopy (60%). The mean detection time for smear-positive and smear-negative samples was 12.5 and 14 days in MGIT-960 and 18 and 25 days for L-J method, respectively. The FASTPlaque failed to detect mycobacteria from the paucibacillary samples. The contamination rates for MGIT-960, L-J, and FASTPlaque assays were 4, 8 and 10%, respectively. The best correlation with mycobacterial load in the specimen was observed in BACTEC-MGIT-960 showing 66.6% detection rate in paucibacillary, 83.3% in 1+ samples, and 100% in 2+ and 3+ samples. Out of the 150 patients, 140 (93.3%) could be diagnosed by one or more nonmolecular methods. Therefore, it could be concluded that combination of three or more in vitro diagnostic methods will have acceptable detection level. | 18,803,271 |
Flow cytometric quantitation of natural killer cells and T lymphocytes expressing T-cell receptors alpha/beta and gamma/delta is not helpful in distinguishing benign from malignant body cavity effusions. | Quantitation of natural killer (NK) cells in benign and malignant effusions has yielded conflicting results in the past. Studies have claimed higher, lower, and essentially equal percentages of NK cells for benign and malignant effusions. In addition, virtually no literature exists on the numbers and distribution of T lymphocytes expressing T-cell receptor alpha/beta (TCR alpha/beta) and T-cell receptor gamma/delta (TCR gamma/delta) in body effusions. Using multicolor flow cytometry and sequential gating techniques, NK cells and T lymphocytes expressing TCR alpha/beta and TCR gamma/delta were identified and quantitated in 30 benign and 30 malignant effusions. No significant difference in percentage of NK cells was found between benign and malignant effusions. The absolute number per miroliter of CD16(+)CD56(+) NK cells was higher in malignant than in benign effusions, but only at a borderline level of statistical significance. T cells expressing TCR alpha/beta far outnumbered those expressing TCR gamma/delta in all effusions, a distribution similar to that in normal adult peripheral blood and lymphoid tissue. The percentages and absolute numbers of these T-cell subsets were the same in benign and malignant effusions. Enumeration of NK cells and of T lymphocytes expressing TCR alpha/beta or TCR gamma/delta in human body effusions is not helpful in attempting to distinguish between benign and malignant effusions. Values for the two T-lymphocyte subsets in human effusions are, to our knowledge, established for the first time by flow cytometric determination. | 18,803,280 |
NOD2 plays an important role in the inflammatory responses of microglia and astrocytes to bacterial CNS pathogens. | While glial cells are recognized for their roles in maintaining neuronal function, there is growing appreciation that resident central nervous system (CNS) cells initiate and/or augment inflammation following trauma or infection. We have recently demonstrated that microglia and astrocytes constitutively express nucleotide-binding oligomerization domain-2 (NOD2), a member of the novel nucleotide-binding domain leucine-rich repeat region containing a family of proteins (NLR) that functions as an intracellular receptor for a minimal motif present in all bacterial peptidoglycans. In this study, we have confirmed the functional nature of NOD2 expression in astrocytes and microglia and begun to determine the relative contribution that this NLR makes in inflammatory CNS responses to clinically relevant bacterial pathogens. We demonstrate the increased association of NOD2 with its downstream effector molecule, Rip2 kinase, in primary cultures of murine microglia and astrocytes following exposure to bacterial antigens. We show that this cytosolic receptor underlies the ability of muramyl dipeptide to augment the production of inflammatory cytokines by glia following exposure to specific ligands for disparate Toll-like receptor homologues. In addition, we demonstrate that NOD2 is an important component in the in vitro inflammatory responses of resident glia to N. meningitidis and B. burgdorferi antigens. Finally, we have established that NOD2 is required, at least in part, for the astrogliosis, demyelination, behavioral changes, and elevated inflammatory cytokine levels observed following in vivo infection with these pathogens. As such, we have identified NOD2 as an important component in the generation of damaging CNS inflammation following bacterial infection. | 18,803,303 |
Biology and pathology of nonmyelinating Schwann cells. | The CNS contains relatively few unmyelinated nerve fibers, and thus benefits from the advantages that are conferred by myelination, including faster conduction velocities, lower energy consumption for impulse transmission, and greater stability of point-to-point connectivity. In the PNS many fibers or regions of fibers the Schwann do not form myelin. Examples include C fibers nociceptors, postganglionic sympathetic fibers, and the Schwann cells associated with motor nerve terminals at neuromuscular junctions. These examples retain a degree of plasticity and a capacity to sprout collaterally that is unusual in myelinated fibers. Nonmyelin-forming Schwann cells, including those associated with uninjured fibers, have the capacity to act as the "first responders" to injury or disease in their neighborhoods. | 18,803,315 |
Interactions between Schwann cells and macrophages in injury and inherited demyelinating disease. | In this article we first discuss the factors that regulate macrophage recruitment, activation, and myelin phagocytosis during Wallerian degeneration and some of the factors involved in the termination of inflammation at the end of the period of Wallerian degeneration after peripheral nerve injuries. In particular, we deal with the early events that trigger chemokine and cytokine expression; the role of phospholipase A(2) in initiating the breakdown of compact myelin, and chemokine, cytokine expression; and the role of MCP-1, MIP-1alpha, and IL-1beta in macrophage recruitment and myelin phagocytosis. We also discuss how inflammation may be switched off and the recently identified role of the Nogo receptor on activated macrophages in the clearance of these cells from the injured nerve. In the second half of the article we focus on the role of certain Schwann cell borne cytokines and chemokines, such as M-CSF and MCP-1 as well as intracellular signaling that regulate their expression in animal models of inherited demyelinating disease. Additionally, we present the preservation of sensory nerves fibers from macrophage attack in these animal models as a challenging paradigm for the development of putative treatment approaches. Finally, we also discuss the similarities and differences in these Schwann cell-macrophage responses in injury-induced Wallerian degeneration and inherited demyelinating diseases. Knowledge of the molecular mechanisms underlying Schwann cell-macrophage interaction under pathological conditions is an important prerequisite to develop effective treatment strategies for various peripheral nerve disorders. | 18,803,324 |
Detecting signals of opioid analgesic abuse: application of a spatial mixed effect poisson regression model using data from a network of poison control centers. | The recent rise in the non-medical use of opioid analgesics in the US has underscored the importance of comprehensive post-marketing surveillance of these products. To assist pharmacovigilance efforts, we developed a methodology for detecting geo-specific "signals" of potential outbreaks of prescription drug abuse by 3-digit ZIP (3DZ) code. The number of intentional exposure calls involving nine specific opioid analgesics were obtained from eight regional poison control centers between first quarter 2003 and fourth quarter 2004. The unit of analysis was a combination of drug-quarter/year-3DZ. We fitted an empirical Bayes mixed effects Poisson-Gamma regression model that adjusted for differences across 3DZs in opioid analgesic exposure. A relative report rate (RR) >or=3 at a probability of >0.95 was the signal threshold criterion. A total of 15,769 valid drug-time-3DZ combinations were identified. Of these, 1.9% (n = 294) met the signal threshold criterion. The number of signals generated per drug-quarter/year-3DZ combination ranged from 0 to 13. The largest number of signals were those involving methadone (n = 71), hydrocodone (n = 57), and branded oxycodone extended-release (n = 45). Signals for methadone and branded oxycodone extended-release were predominantly clustered in Appalachia. Hydrocodone-related signals showed less geographic clustering with approximately 26% reported from California, and the remainder from other regions in the US. Our results show marked regional differences in reported abuse of specific opioid analgesics. Additional research is needed to determine the sensitivity and specificity of signals obtained using this spatial mixed effect Poisson regression model. | 18,803,336 |
An integrated system for planning, navigation and robotic assistance for skull base surgery. | We developed an image-guided robot system to provide mechanical assistance for skull base drilling, which is performed to gain access for some neurosurgical interventions, such as tumour resection. The motivation for introducing this robot was to improve safety by preventing the surgeon from accidentally damaging critical neurovascular structures during the drilling procedure. We integrated a Stealthstation navigation system, a NeuroMate robotic arm with a six-degree-of-freedom force sensor, and the 3D Slicer visualization software to allow the robotic arm to be used in a navigated, cooperatively-controlled fashion by the surgeon. We employed virtual fixtures to constrain the motion of the robot-held cutting tool, so that it remained in the safe zone that was defined on a preoperative CT scan. We performed experiments on both foam skull and cadaver heads. The results for foam blocks cut using different registrations yielded an average placement error of 0.6 mm and an average dimensional error of 0.6 mm. We drilled the posterior porus acusticus in three cadaver heads and concluded that the robot-assisted procedure is clinically feasible and provides some ergonomic benefits, such as stabilizing the drill. We obtained postoperative CT scans of the cadaver heads to assess the accuracy and found that some bone outside the virtual fixture boundary was cut. The typical overcut was 1-2 mm, with a maximum overcut of about 3 mm. The image-guided cooperatively-controlled robot system can improve the safety and ergonomics of skull base drilling by stabilizing the drill and enforcing virtual fixtures to protect critical neurovascular structures. The next step is to improve the accuracy so that the overcut can be reduced to a more clinically acceptable value of about 1 mm. | 18,803,337 |
Weight loss and isotopic shifts for water drops frozen on a liquid nitrogen surface. | A liquid nitrogen freezing method was used to collect raindrops for the determination of isotope-size distribution. Water drops that fall onto a surface of liquid nitrogen stay suspended for 10 to 20 s, until their temperature reaches the Leidenfrost point (126 K). As their temperature falls to the freezing point, they release their heat by thermal conduction. At the freezing point, latent heat of fusion is released, along with a significant loss of water. After freezing completely, the ice droplets stay suspended, cooling by thermal conduction until they reach the Leidenfrost point. They then lose buoyancy and start sinking. Consistent isotopic changes of 1.5 +/- 0.4 and 0.33 +/- 0.05 per thousand for hydrogen and oxygen, respectively, were found for droplets with radii between 1.0 and 1.5 mm. Isotope fractionation appeared to occur at the same time as water loss, as the droplets were freezing, in what was probably a kinetic effect. | 18,803,342 |
Enrichment of low molecular weight serum proteins using acetonitrile precipitation for mass spectrometry based proteomic analysis. | A rapid acetonitrile (ACN)-based extraction method has been developed that reproducibly depletes high abundance and high molecular weight proteins from serum prior to mass spectrometric analysis. A nanoflow liquid chromatography/tandem mass spectrometry (nano-LC/MS/MS) multiple reaction monitoring (MRM) method for 57 high to medium abundance serum proteins was used to characterise the ACN-depleted fraction after tryptic digestion. Of the 57 targeted proteins 29 were detected and albumin, the most abundant protein in serum and plasma, was identified as the 20th most abundant protein in the extract. The combination of ACN depletion and one-dimensional nano-LC/MS/MS enabled the detection of the low abundance serum protein, insulin-like growth factor-I (IGF-I), which has a serum concentration in the region of 100 ng/mL. One-dimensional sodium dodecyl sulfate/polyacrylamide gel electrophoresis (SDS-PAGE) analysis of the depleted serum showed no bands corresponding to proteins of molecular mass over 75 kDa after extraction, demonstrating the efficiency of the method for the depletion of high molecular weight proteins. Total protein analysis of the ACN extracts showed that approximately 99.6% of all protein is removed from the serum. The ACN-depletion strategy offers a viable alternative to the immunochemistry-based protein-depletion techniques commonly used for removing high abundance proteins from serum prior to MS-based proteomic analyses. | 18,803,344 |
Biological impact of hepatitis B virus X-hepatitis C virus core fusion gene on human hepatocytes. | To investigate the biological impact of hepatitis B virus X- hepatitis C virus core (HBV X-HCV C) fusion gene on hepatoma cells. The recombinant adenoviruses Ad-XC, Ad-X and Ad-C expressing HBV X-HCV C fusion gene, HBV X gene and HCV C gene were constructed, respectively. Hepatoma cells were infected with different recombinant adenoviruses. MTT, colony-forming experiment, FCM, TUNEL assay were performed to observe the biological impact of the HBV X-HCV C fusion gene on liver cells. MTT showed that the Ad-XC group cells grew faster than the other group cells. Colony-forming experiment showed that the colony-forming rate for the Ad-XC group cells was significantly higher than that for the other group cells. FCM analysis showed that Ad-XC/Ad-X/Ad-C infection enhanced the progression of G1-->S phase in the HepG2 cell cycle. The apoptosis index of the Ad-XC, Ad-X, Ad-C group cells was significantly lower than that of the Ad0 and control group cells. Semi-quantitative RT-PCR showed that the expression level of c-myc was the highest in Ad-XC infected cells. Tumor formation was found at the injected site of mice inoculated with Ad-XC-infected LO2 cells, but not in control mice. Ad-XC, Ad-X and Ad-C facilitate the proliferation activity of HepG2 cells and inhibit their apoptosis in vitro. The effect of Ad-XC is significantly stronger than that of Ad-X and Ad-C. Up-regulation of c-myc may be one of the mechanisms underlying the synergism of HBV X and HCV C genes on hepatocarcinogenesis in athymic nude mice. | 18,803,352 |
"Rescue" regimens after Helicobacter pylori treatment failure. | Helicobacter pylori (H pylori) infection is the main cause of gastritis, gastroduodenal ulcer disease, and gastric cancer. After more than 20 years of experience in H pylori treatment, in my opinion, the ideal regimen to treat this infection is still to be found. Currently, apart from having to know first-line eradication regimens well, we must also be prepared to face treatment failures. Therefore, in designing a treatment strategy we should not focus on the results of primary therapy alone, but also on the final (overall) eradication rate. The choice of a "rescue" treatment depends on which treatment is used initially. If a clarithromycin-based regimen was used initially, a subsequent metronidazole-based treatment (quadruple therapy) may be used afterwards, and then a levofloxacin-based combination would be a third "rescue" option. Alternatively, it has recently been suggested that levofloxacin-based rescue therapy constitutes an encouraging second-line strategy, representing an alternative to quadruple therapy in patients with previous PPI-clarithromycin-amoxicillin failure, with the advantage of efficacy, simplicity and safety. In this case, a quadruple regimen may be reserved as a third-line rescue option. Finally, rifabutin-based rescue therapy constitutes an encouraging empirical fourth-line strategy after multiple previous eradication failures with key antibiotics such as amoxicillin, clarithromycin, metronidazole, tetracycline, and levofloxacin. Even after two consecutive failures, several studies have demonstrated that H pylori eradication can finally be achieved in almost all patients if several rescue therapies are consecutively given. Therefore, the attitude in H pylori eradication therapy failure, even after two or more unsuccessful attempts, should be to fight and not to surrender. | 18,803,350 |
Is there a role for Tc-99m (V) DMSA scintigraphy in ischemic colitis? | To evaluate the role of pentavalent Tc-99m dimercaptosuccinic acid [Tc-99m (V) DMSA] in the diagnosis of ischemic colitis. Fourteen patients with endoscopically and histologically confirmed ischemic colitis were included in the study. Tc-99m (V) DMSA scintigraphy was performed within 2 d after colonoscopy. Images were considered positive when an area of increased activity was observed in the region of interest and negative when no abnormal tracer uptake was detected. In 3 out of the 14 patients, Tc-99m (V) DMSA images showed moderate activity in the bowel. The scintigraphic results corresponded with the endoscopic findings. In the other 11 patients, no abnormal tracer uptake was detected in the abdomen. Besides the limited number of patients, Tc-99m (V) DMSA could not be considered as a useful imaging modality for the evaluation of ischemic colitis. | 18,803,355 |
Development of autoimmune hepatitis type 1 after pulsed methylprednisolone therapy for multiple sclerosis: a case report. | A 43-year-old woman with multiple sclerosis (MS) was treated with pulsed methylprednisolone and interferon beta at a hospital. Four weeks after initiating treatment, liver dysfunction occurred and she was referred and admitted to our hospital. Clinical and laboratory findings were consistent with and fulfilled the criteria for drug-induced hepatitis, but not for autoimmune hepatitis (AIH). She was successfully treated with corticosteroids. As ataxia developed after 1 year, she was treated with pulsed methylprednisolone for 3 d, then readmitted to our hospital when liver dysfunction occurred. Clinical and laboratory findings led to the diagnosis of AIH. To the best of our knowledge, this is the second case of AIH developed after pulsed methylprednisolone for MS. | 18,803,363 |
Self-assembly of alpha-helical coiled coil nanofibers. | The alpha-helical coiled coil is one of the best-studied and most well-understood protein folding motifs. In particular, the coiled coil can be made to self-assemble into a nanofibrous architecture with many potential applications in biomimetic engineering and elsewhere. The key to the assembly of such nanofibers has been the formation of "sticky ended" dimers through careful selection of electrostatically charged amino acids. In this work, we demonstrate for the first time that sticky ended dimers are not a prerequisite for alpha-helical coiled coil nanofiber formation. In contrast, we show that blunt-ended dimers are able to form nanofibers with a uniform diameter of 4 nm while being hundreds of nanometers in length. Furthermore, the length and lateral packing can be controlled through selection of amino acids not involved in the coiled coil interface. | 18,803,383 |
From a paramagnetic, mononuclear supersulfidonickel(II) complex to a diamagnetic dimer with a four-sulfur two-electron bond. | The first isolable "side-on" supersulfidonickel(II) complex 1(1) with the elusive S2-. ligand has been synthesized by facile oxidation of the corresponding nickel(I) precursor [LNi] with elemental sulfur. Remarkably, paramagnetic 1(1) associates voluntarily to give the diamagnetic dimer 1(2) with a four-sulfur two-electron bond as proven by X-ray diffraction analysis, spectroscopic measurements (1H NMR, EPR, SQUID), and DFT calculations. Gentle sulfur transfer of 1(1) to Ph3P or its reaction with [LNi] affords solely the genuine disulfide complex 3 having a Ni2(mu-mu2:mu2-S2) core. | 18,803,388 |
E113 is required for the efficient photoisomerization of the unprotonated chromophore in a UV-absorbing visual pigment. | Protonation of the retinal Schiff base chromophore is responsible for the absorption of visible light and is stabilized by the counterion residue E113 in vertebrate visual pigments. However, this residue is also conserved in vertebrate UV-absorbing visual pigments (UV pigments) which have an unprotonated Schiff base chromophore. To elucidate the role played by this residue in the photoisomerization of the unprotonated chromophore in UV pigments, we measured the quantum yield of the E113Q mutant of the mouse UV cone pigment (mouse UV). The quantum yield of the mutant was much lower than that of the wild type, indicating that E113 is required for the efficient photoisomerization of the unprotonated chromophore in mouse UV. Introduction of the E113Q mutation into the chicken violet cone pigment (chicken violet), which has a protonated chromophore, caused deprotonation of the chromophore and a reduction in the quantum yield. On the other hand, the S90C mutation in chicken violet, which deprotonated the chromophore with E113 remaining intact, did not significantly affect the quantum yield. These results suggest that E113 facilitates photoisomerization in both UV-absorbing and visible light-absorbing visual pigments and provide a possible explanation for the complete conservation of E113 among vertebrate UV pigments. | 18,803,408 |
Quantum-interference-controlled molecular electronics. | Quantum interference in coherent transport through single molecular rings may provide a mechanism to control the current in molecular electronics. We investigate its applicability, using a single-particle Green function method combined with ab initio electronic structure calculations. We find that the quantum interference effect (QIE) is strongly dependent on the interaction between molecular pi-states and contact sigma-states. It is masked by sigma tunneling in small molecular rings with Au leads, such as benzene, due to strong pi-sigma hybridization, while it is preserved in large rings, such as [18]annulene, which then could be used to realize quantum interference effect (QIE) transistors. | 18,803,424 |
Oxygen consumption during functional electrical stimulation-assisted exercise in persons with spinal cord injury: implications for fitness and health. | A lesion in the spinal cord leads in most cases to a significant reduction in active muscle mass, whereby the paralysed muscles cannot contribute to oxygen consumption (VO2) during exercise. Consequently, persons with spinal cord injury (SCI) can only achieve high VO2 values by excessively stressing the upper body musculature, which might increase the risk of musculoskeletal overuse injury. Alternatively, the muscle mass involved may be increased by using functional electrical stimulation (FES). FES-assisted cycling, FES-cycling combined with arm cranking (FES-hybrid exercise) and FES-rowing have all been suggested as candidates for cardiovascular training in SCI. In this article, we review the levels of VO2 (peak [VO2peak] and sub-peak [VO2sub-peak]) that have been reported for SCI subjects using these FES exercise modalities. A systematic literature search in MEDLINE, EMBASE, AMED, CINAHL, SportDiscus and the authors' own files revealed 35 studies that reported on 499 observations of VO2 levels achieved during FES-exercise in SCI. The results show that VO2peak during FES-rowing (1.98 L/min, n = 17; 24.1 mL/kg/min, n = 11) and FES-hybrid exercise (1.78 L/min, n = 67; 26.5 mL/kg/min, n = 35) is considerably higher than during FES-cycling (1.05 L/min, n = 264; 14.3 mL/kg/min, n = 171). VO2sub-peak values during FES-hybrid exercise were higher than during FES-cycling. FES-exercise training can produce large increases in VO2peak; the included studies report average increases of +11% after FES-rowing training, +12% after FES-hybrid exercise training and +28% after FES-cycling training. This review shows that VO2 during FES-rowing or FES-hybrid exercise is considerably higher than during FES-cycling. These observations are confirmed by a limited number of direct comparisons; larger studies to test the differences in effectiveness of the various types of FES-exercise as cardiovascular exercise are needed. The results to date suggest that FES-rowing and FES-hybrid are more suited for high-intensity, high-volume exercise training than FES-cycling. In able-bodied people, such exercise programmes have shown to result in superior health and fitness benefits. Future research should examine whether similar high-intensity and high-volume exercise programmes also give persons with SCI superior fitness and health benefits. This kind of research is very timely given the high incidence of physical inactivity-related health conditions in the aging SCI population. | 18,803,435 |
Paclitaxel and docetaxel in the treatment of breast cancer. | Paclitaxel and docetaxel are considered fundamental drugs in the treatment of breast cancer. To review the current role of taxanes in the treatment breast cancer, with emphasis on data from randomized trials comparing the two taxanes. We have reviewed the available evidence in the literature to gauge the results of therapy of early and advanced breast cancer with taxanes. Clinically benefits were first shown in metastatic setting. More recently, benefits have also been seen in the therapy of early-stage disease. It seems reasonable to consider either drug as standard treatment for node-positive early stage or metastatic breast cancer. Future studies should explore the optimal way of combining taxanes with novel biological and cytotoxic drugs. Based on existing evidence, clinicians should choose a taxane-based regimen for their patients, according to clinical activity, toxicity profile, pharmacokinetics, and a dosing schedule that best meets the therapeutic needs and convenience. | 18,803,448 |
Pharmacoeconomics of entecavir treatment for chronic hepatitis B. | Entecavir is a new antiviral agent for chronic hepatitis B virus (HBV) infection with potent HBV suppression and a low rate of viral resistance. To review published studies on the pharmacoeconomics of entecavir for treatment of chronic HBV. A literature search on Medline and Embase over the period of 1998 - 2008 was performed in April 2008 using keywords 'entecavir' and 'cost'. Four studies comparing the cost effectiveness of entecavir with lamivudine and/or adefovir for treatment with chronic HBV infection using either decision tree or Markov modeling were reviewed. All four studies showed that entecavir was cost-effective in the treatment of chronic HBV with the incremental cost per QALY (quality-adjusted life-year) gained below the commonly accepted benchmark. The results are mainly due to the lower complication rates and better quality of life of patients using entecavir which can offset the higher acquisition cost of the drug. Patient characteristics, comparing agents and model assumptions were different among the four studies and they should be taken into account when applying the results to real life situations. | 18,803,453 |
Mitiglinide: a rapid- and short-acting non-sulfonylurea insulinotropic agent for the treatment of type 2 diabetic patients. | This review article deals with mitiglinide, a rapid-acting non-sulfonylurea insulinotropic agent for the treatment of type 2 diabetic patients. Attention is drawn to the background history of mitiglinide, its chemistry, its determination in plasma, its metabolic pathway, preclinical investigations conducted - either in vitro on the uptake of mitiglinide by pancreatic islets, the effects of mitiglinide on ionic channels, its insulinotropic action and its effect on glucose metabolism in hepatocytes and its cardiovascular effects, or in vivo in animals - as well as to clinical investigations with mitiglinide. | 18,803,455 |
Dynamic intracellular distribution of Eaf2 and its potential involvement in UV-Induced DNA damage response. | Eaf2 encodes a tumor suppressor that plays multiple functions in transcriptional activation, apoptosis, and embryonic development. In this study, we utilized GFP-EAF2 fusion protein to describe the dynamic subcellular movement of Eaf2. GFP-EAF2 is preferentially localized to the nucleus, and in the presence of ELL, it accumulates in nuclear speckles. However, Eaf2 is an unstable nuclear protein whose stability is affected by serum. Further, we provided first evidence that nuclear distribution of Eaf2 is responsive to DNA damage. Following UV irradiation, Eaf2 is relocalized to the nucleolus, suggesting a possible functional involvement of Eaf2 in DNA damage response. | 18,803,460 |
Carotid angioplasty and stenting under protection: advantages and drawbacks. | Carotid stenosis is responsible for approximately 30% of strokes, and carotid endarterectomy is considered to be the gold-standard treatment. Carotid angioplasty and stenting (CAS) has been proposed as an alternative to surgery but the risk of neurological complications and brain embolism remains the major drawback to this procedure. Embolic protection devices (EPDs), which retain particles and debris generated during the procedure, have been proposed to reduce the frequency of neurological complications. Three types of EPD have been developed: distal occlusion balloon, distal filters and proximal protection devices. Preliminary clinical results indicate that the routine use of an EPD along with specifically designed flexible stents, increasing skills of the interventionist and appropriate drugs combine to reduce ischemic neurological complications and can achieve similar results to the best surgical series, particularly in high surgical risk patients. Recent prospective, multicenter controlled trials and registries evaluating CAS with EPD have demonstrated that the CAS results are, at least, not inferior to surgery for patients at high risk for surgery (Stenting and Angioplasty with Protection in Patients at High Risk for Endarterectomy study) and in symptomatic patients (Stent Supported Percutaneous Angioplasty of the Carotid Artery versus Endarterectomy study). However, all protection devices are not equivalent and have some drawbacks. Advantages and disadvantages of each EPD will be analyzed in this review, allowing a good choice of the EPD depending on the patient and the lesion. Nevertheless, there is now a consensus among specialists to perform all CAS with EPD. EPDs have become an integral part of CAS and the routine use of EPDs seems beneficial, leading to a 60% reduction of brain embolisms. | 18,803,470 |
Strategies and applications for incorporating physical and chemical signal gradients in tissue engineering. | From embryonic development to wound repair, concentration gradients of bioactive signaling molecules guide tissue formation and regeneration. Moreover, gradients in cellular and extracellular architecture as well as in mechanical properties are readily apparent in native tissues. Perhaps tissue engineers can take a cue from nature in attempting to regenerate tissues by incorporating gradients into engineering design strategies. Indeed, gradient-based approaches are an emerging trend in tissue engineering, standing in contrast to traditional approaches of homogeneous delivery of cells and/or growth factors using isotropic scaffolds. Gradients in tissue engineering lie at the intersection of three major paradigms in the field-biomimetic, interfacial, and functional tissue engineering-by combining physical (via biomaterial design) and chemical (with growth/differentiation factors and cell adhesion molecules) signal delivery to achieve a continuous transition in both structure and function. This review consolidates several key methodologies to generate gradients, some of which have never been employed in a tissue engineering application, and discusses strategies for incorporating these methods into tissue engineering and implant design. A key finding of this review was that two-dimensional physicochemical gradient substrates, which serve as excellent high-throughput screening tools for optimizing desired biomaterial properties, can be enhanced in the future by transitioning from two dimensions to three dimensions, which would enable studies of cell-protein-biomaterial interactions in a more native tissue-like environment. In addition, biomimetic tissue regeneration via combined delivery of graded physical and chemical signals appears to be a promising strategy for the regeneration of heterogeneous tissues and tissue interfaces. In the future, in vivo applications will shed more light on the performance of gradient-based mechanical integrity and signal delivery strategies compared to traditional tissue engineering approaches. | 18,803,499 |
Rabies in China: an update. | Human rabies cases in China have continued to increase in recent years, reaching a new peak in 2007. Parallel with an increase in human rabies deaths, a number of animal species with rabies have been reported in the majority of rabies-endemic areas. In this report, the occurrence, status, and control of rabies in both humans and animals are reviewed. Vaccines and immunoglobulin for human and animal use and postexposure prophylaxis for human are also summarized. The current strategies for rabies elimination in China are presented. | 18,803,503 |
Generation and characterization of monoclonal antibodies to mTOR kinase. | Abstract Mammalian target of rapamycin (mTOR) is a serine/threonine kinase that plays a critical role in the regulation of basic cellular functions, including cellular growth and proliferation. In this study we describe the generation and characterization of novel monoclonal antibodies directed against mTOR protein kinase. A GST-tagged fragment of mTOR expressed in bacteria was used as an antigen. Antibody-producing hybridoma cells were obtained by fusing SP2/0 myeloma cells with splenocytes from immunized mice. Anti-mTOR antibody-producing hybridoma cell lines were first identified by enzyme-linked immunosorbent assay and then subcloned by limiting dilution. Antibodies produced by selected clones were further tested for their reactivity towards the GST/mTOR 1334-1504 recombinant protein. Furthermore, antibody produced by F11 clone was shown to recognize specifically mTOR in different tissues and cell lines in Western blotting, immunoprecipitation, and immunohistochemistry. In addition, mTOR F11 antibody was suitable for immunoprecipitating and testing mTOR activity in in vitro kinase assay. In summary, generated antibodies will be useful for investigating mTOR signaling complexes in normal and pathological states. | 18,803,507 |
Laparoscopic total extraperitoneal inguinal hernia repair under spinal anesthesia: a study of 480 patients. | Laparoscopic total extraperitoneal inguinal hernia repair (TEP) is conventionally performed under general anesthesia (GA), and regional anesthesia is usually preferred in patients where GA is contraindicated. In this paper, we present our experience of over 8 years of using spinal anesthesia (SA) as the first choice with the contention that it is a better alternative to GA. SA was used in 480 patients over the last 8 years, and 464 patients underwent unilateral TEP. Strangulated and obstructed hernia patients were excluded, but irreducible hernia patients were included. Sedation was given if required, and the conversion to GA was done in patients not responding to sedation or with failure of SA. Comparative control included TEP performed under GA in our initial 49 patients. Three (0.63%) patients required a conversion to GA. Hypotension requiring support was recorded in 75 (15.63%) patients. Postoperatively, 2.08% (10) patients had vomiting, as compared to 30.61% (15 patients) in patients administered GA. In all, 35.83% (172) of patients required injectable diclofenac for their abdominal pain within 2 hours postoperatively, and oral analgesic was required in 301 (62.71%) patients within the first 24 hours, while 89.80% (44) patients operated an under GA required injectable analgesics in the immediate postoperative period and subsequent oral analgesia request was the same as in patients with SA. Postural headache, persisting for an average of 2.6 days, was seen in 25 (5.21%) patients postoperatively. Average time to discharge was 2.3 days. Kernofsky's performance status showed a 98.6% satisfaction level in patients. TEP done under SA has a number of advantages over GA and should be used routinely. | 18,803,509 |
A 5- versus 3-day course of oral corticosteroids for children with asthma exacerbations who are not hospitalised: a randomised controlled trial. | To determine whether a 5-day course of oral prednisolone is superior to a 3-day course in reducing the 2-week morbidity of children with asthma exacerbations who are not hospitalised. Double-blind randomised controlled trial of asthma outcomes following a 5-day course of oral prednisolone (1 mg/kg) compared with a 3-day course of prednisolone plus placebo for 2 days. Participants were children aged 2-15 years who presented to the emergency departments of three Queensland hospitals between March 2004 and February 2007 with an acute exacerbation of asthma, but were not hospitalised. Sample size was defined a priori for a study power of 90%. Difference in proportion of children who were symptom-free at Day 7, as measured by intention-to-treat (ITT) and per-protocol analysis; quality of life (QOL) on Days 7 and 14. 201 children were enrolled, and there was an 82% completion rate. There was no difference between groups in the proportion of children who were symptom-free (observed difference, 0.04 [95% CI, - 0.09 to 0.18] by ITT analysis; 0.04 [95% CI, - 0.17 to 0.09] by per-protocol analysis). There was also no difference between groups in QOL (P = 0.42). The difference between groups for the primary outcome was within the equivalence range calculated post priori. A 5-day course of oral prednisolone confers no advantage over a 3-day course for children with asthma exacerbations who are not hospitalised. Australian Clinical Trials Registry ACTRN012605000305628. | 18,803,532 |
High levels of confusion for cholesterol awareness campaigns. | Earlier this year, two industry-sponsored advertising campaigns for cholesterol awareness that target the general public were launched in Australia. These campaigns aimed to alert the public to the risks associated with having high cholesterol and encouraged cholesterol testing for wider groups than those specified by the National Heart Foundation. General practitioners should be aware of the potential for the two campaigns to confuse the general public as to who should be tested, and where. The campaign sponsors (Unilever Australasia and Pfizer) each have the potential to benefit by increased market share for their products, and increased profits. These disease awareness campaigns are examples of what is increasingly being termed "condition branding" by pharmaceutical marketing experts. | 18,803,537 |
The viability of Australia's teaching hospitals. | In a now diverse range of teaching hospitals striving to excel, excellence in research should be prioritised. | 18,803,538 |
Noncontact mapping of the heart: how and when to use. | The noncontact mapping system is a new tool for electrophysiologic study and radiofrequency ablation. The mode of operation includes single beat, three-dimensional, high-density mapping. Careful analysis of unipolar electrograms and isopotential maps are essential to understand the mechanism of the arrhythmia. Radiofrequency catheter ablation guided by this system is effective in curing patients of their tachycardias. | 18,803,565 |
Description and phylogeny of Ceratomyxa anko sp. n. and Zschokkella lophii sp. n. from the Japanese anglerfish, Lophius litulon (Jordan). | Two new species of myxozoans from the Japanese anglerfish, Lophius litulon, are described using myxospore morphology and small subunit rDNA sequences. Ceratomyxa anko sp. n. is a parasite of the gall bladder and had a prevalence of 57%. Mature spores of C. anko sp. n. are arcuate to crescent shaped with valves tapering to rounded tips. A prominent sutural line runs centrally between the round adjacent polar capsules containing the polar filament coiled two to three times. Spore measurements: length 10.8 (9.7-11.9) microm, width 41.9 (36.9-47.2) microm, polar capsule diameter 4.6 (4.1-5.3) microm. Ceratomyxa anko sp. n. can be distinguished from other Ceratomyxa spp. due to its spore dimensions and shape. Zschokkella lophii sp. n. is a parasite of the urinary bladder and had a prevalence of 70%. Mature spores are ellipsoidal to semicircular with bluntly pointed ends. The sutural line is curved or sinuous and the valves have no discernable surface ornamentation. Two almost spherical polar capsules are located separately in the ends of the spore, opening in almost opposite directions and contain the polar filament with five coils. Spore measurements: length 20.1 (16.8-24.0) microm, width 14.9 (12.7-16.8) microm, polar capsule diameter 5.1 (3.6-5.8) microm. Zschokkella lophii sp. n. can be distinguished from other Zschokkella spp. due to the terminal opening of the polar capsules within the spores and the site of infection within the host fish. In the phylogenetic analyses, C. anko sp. n. grouped with other members of the same genus forming a monophyly. Zschokkella lophii sp. n. forms a discrete clade with another Zschokkella sp. that infects the urinary bladder of marine fish. This grouping forms a sister clade to one containing members of the genus Parvicapsula, all of which are parasites of the urinary system in marine fish. | 18,803,583 |
The effects of water velocity on the Ceratomyxa shasta infectious cycle. | Ceratomyxa shasta is a myxozoan parasite identified as a contributor to salmon mortality in the Klamath River, USA. The parasite has a complex life cycle involving a freshwater polychaete, Manayunkia speciosa and a salmonid. As part of ongoing research on how environmental parameters influence parasite establishment and replication, we designed a laboratory experiment to examine the effect of water flow (velocity) on completion of the C. shasta infectious cycle. The experiment tested the effect of two water velocities, 0.05 and 0.01 m s(-1), on survival and infection of M. speciosa as well as transmission to susceptible rainbow trout and comparatively resistant Klamath River Chinook salmon. The faster water velocity facilitated the greatest polychaete densities, but the lowest polychaete infection prevalence. Rainbow trout became infected in all treatments, but at the slower velocity had a shorter mean day to death, indicating a higher infectious dose. Infection was not detected in Chinook salmon even at a dose estimated to be as high as 80,000 actinospores per fish. The higher water velocity resulted in lower C. shasta infection prevalence in M. speciosa and decreased infection severity in fish. Another outcome of our experiment is the description of a system for maintaining and infecting M. speciosa in the laboratory. | 18,803,584 |
Gene expression profile of Huh-7 cells expressing hepatitis C virus genotype 1b or 3a core proteins. | The liver disease expression in chronic hepatitis C patients is variable and may partially depend on the sequence of the infecting viral genotype. To identify some hepatitis C virus (HCV) genotype-specific virus-host interactions potentially leading to clinically significant consequences. We compared the gene expression profile of Huh-7 cells transiently expressing the core protein of HCV genotype 1b and 3a using microarray technology. Thirty-two genes were overexpressed in Huh-7 transfected with the HCV genotype 1b core protein and 57 genes in cells transfected with the genotype 3a core protein. On the other hand, we found 20 genes downregulated by core 1b and 31 genes by core 3a. These included genes involved in lipid transport and metabolism, cell cycle, immune response and insulin signalling. The expression of HCV core proteins of different genotypes leads to a specific gene expression profile. This may account for the variable disease expression associated with HCV infection. | 18,803,589 |
Neural mechanisms underlying the processing of Chinese and English words in a word generation task: an event-related potential study. | Event-related brain potentials (ERPs) were used to examine the spatiotemporal cortical activation patterns underlying Chinese and English word generation (forming a new word by adding a stroke or a letter to an old Chinese or English word) for low- and high-proficiency Chinese-English bilinguals. The results revealed that early visual perceptual processing and word identification were similar between the two languages for the N120 and P220 waveforms. However, a greater negative potential (N250-350) was associated with Chinese words than with English words between 250 and 350 ms. Subsequently, for fluent Chinese bilinguals, Chinese words elicited a more positive ERP deflection (LPC) than did English words between 350 and 800 ms. The differences in ERP components between Chinese and English words indicates that there might be a real difference in the processing demands between these languages, and that the processing of English might be affected by the proficiency of the second language. | 18,803,601 |
High frequency jet ventilation through the laryngeal mask airway in a critically obstructed airway. | A 72 year-old man with an anticipated difficult airway secondary to a large, obstructing supraglottic tumour was scheduled for a panendoscopy. An elective pre-induction transtracheal catheter was placed to allow oxygenation if airway maintenance proved difficult. Following induction of anaesthesia, tracheal intubation was impossible and ventilation via both a facepiece and a laryngeal mask airway became progressively more difficult. An emergency tracheostomy was attempted whilst oxygenation was maintained with transtracheal jet ventilation, but the position of the transtracheal catheter made tracheostomy impossible. The catheter was removed and high frequency jet ventilation was then used via the laryngeal mask airway to maintain oxygenation. To our knowledge, the use of high frequency jet ventilation through the laryngeal mask airway in a critically obstructed airway has not been described before. | 18,803,629 |
Tympanic ossicles and pharyngeal arches. | We have performed a study on 11 human embryos regarding the development of the tympanic ossicles and their relationship with the first pharyngeal arch. After performing measurements to date the embryos and foetuses chronologically, we performed a meticulous dissection of the temporal bones. Subsequently, they were fixed in 10% formol, decalcified with 2% nitric acid, embedded in Paraplast, sectioned in 7-mm sequences and stained with Martin's trichrome technique. In the 21- and 24-mm cranium-raquis (CR) length human embryos, we have observed the head of the malleus and the body of the incus close to Meckel's cartilage, in addition to the handle of the malleus, the long limb of the incus and the stapes. Between them there was a mesenchymal band inside the primordium of the tympanic cavity. In the 27-mm CR embryo, the various components of the malleus and incus were fusing, and in the 30-mm CR embryo the union was complete. From our observations, we can conclude that the malleus and the incus are derived from the first and second pharyngeal arches. | 18,803,631 |
CT-soft tissue window of the cranial abdomen in clinically normal dogs: an anatomical description using macroscopic cross-sections with vascular injection. | The aim of this study was to provide a detailed anatomic atlas of the cranial abdomen by means of computed tomography (CT). Three mature dogs, all mixed breed males, were used. The dogs were sedated, anaesthetized and positioned in sternal recumbency. CT scans from the eighth thoracic vertebra to the fourth lumbar vertebra were performed using a third-generation equipment (TOSHIBA 600HQ scanner) with 1 cm slice thickness. CT-images of the cranial abdomen were taken with soft-tissue window (WL: -14, WW: 658) settings. Dogs were killed and vascular-injection technique was performed: red and blue latex filled the vascular system. Injected dogs were frozen in the same position as used for CT examination and sectioned with an electric bandsaw at 1-cm-thick intervals. The cuts matched as closely as possible to the CT-images. The anatomic sections were compared and studied with the corresponding CT-images, and clinically relevant abdominal anatomic structures were identified and labelled on the corresponding CT-images. The results of our study could be used as a reference for evaluating CT-images of the canine cranial abdomen with abdominal diseases. | 18,803,632 |
Metformin suppresses intestinal polyp growth in ApcMin/+ mice. | Metformin is a biguanide derivative that is widely used in the treatment of diabetes mellitus. One of the pharmacological targets of metformin is adenosine monophosphate-activated protein kinase (AMPK). We investigated the effect of metformin on the suppression of intestinal polyp formation in Apc(Min/+) mice. Administration of metformin (250 mg/kg) did not reduce the total number of intestinal polyp formations, but significantly reduced the number of intestinal polyp formations larger than 2 mm in diameter in Apc(Min/+) mice. To examine the indirect effect of metformin, the index of insulin resistance and serum lipid levels in Apc(Min/+) mice were assessed. These factors were not significantly attenuated by the treatment with metformin, indicating that the suppression of polyp growth is not due to the indirect drug action. The levels of tumor cell proliferation as determined by 5-bromodeoxyuridine and proliferating cell nuclear antigen immunohistochemical staining, and apoptosis, via transferase deoxytidyl uridine end labeling staining, in the polyps of metformin-treated mice were not significantly different in comparison to those of control mice. Gene expression of cyclin D1 and c-myc in intestinal polyps were also not significantly different between those two groups. In contrast, metformin activated AMPK in the intestinal polyps, resulting in the inhibition of the activation of mammalian target of rapamycin, which play important roles in the protein synthesis machinery. Metformin suppressed the polyp growth in Apc(Min/+) mice, suggesting that it may be a novel candidate as a chemopreventive agent for colorectal cancer. | 18,803,638 |
Extended NO analysis in a healthy subgroup of a random sample from a Swedish population. | There is an interest in modelling exhaled nitric oxide (NO). Studies have shown that flow-independent NO parameters i.e. NO of the alveolar region (C(A)NO), airway wall (C(aw)NO), diffusing capacity (D(aw)NO) and flux (J(aw)NO), are altered in several disease states such as asthma, cystic fibrosis, alveolitis and chronic obsmuctive pulmonary disease (COPD). However, values from a healthy population are missing. To calculate NO parameters in a healthy population by collecting NO values at different exhalation flow rates. A random sample from the ECRHS II study was investigated. Among the 281 subjects that had performed a bronchial hyperreactivity (BHR)-test, FEV(1.0), IgE and NO-analyses 89 were found to be healthy. There were no differences in F(E)NO(0.05) or NO parameters between men and women. There were weak correlations between height and both F(E)NO(0.05) (r = 0.23, P = 0.03) and C(aw)NO (r = 0.22, P = 0.04). There was also a correlation between age and C(A)NO (r = 0.28, P = 0.007). When controlled for gender, this correlation was more powerful in women (r = 0.51, P = 0.001) but did not remain for male subjects. Extended NO analysis is a simple non-invasive tool that gives by far more information than F(E)NO(0.05). Based on our results, we suggest that the values for healthy subjects should be considered to fall between the following ranges: F(E)NO(0.05), 10-30 ppb; C(aw)NO, 50-250 ppb; D(aw)NO, 5-15 ml s(-1); J(aw)NO, 0.8-1.6 nl s(-1); and C(A)NO, 0-4 ppb. Values outside these intervals indicate the need for further investigation to exclude a state of disease. | 18,803,639 |
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