title stringlengths 0 1.13k | abstract stringlengths 1 15.7k | PMID int64 22 36.5M |
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Pseudomonas Genome Database: facilitating user-friendly, comprehensive comparisons of microbial genomes. | Pseudomonas aeruginosa is a well-studied opportunistic pathogen that is particularly known for its intrinsic antimicrobial resistance, diverse metabolic capacity, and its ability to cause life threatening infections in cystic fibrosis patients. The Pseudomonas Genome Database (http://www.pseudomonas.com) was originally developed as a resource for peer-reviewed, continually updated annotation for the Pseudomonas aeruginosa PAO1 reference strain genome. In order to facilitate cross-strain and cross-species genome comparisons with other Pseudomonas species of importance, we have now expanded the database capabilities to include all Pseudomonas species, and have developed or incorporated methods to facilitate high quality comparative genomics. The database contains robust assessment of orthologs, a novel ortholog clustering method, and incorporates five views of the data at the sequence and annotation levels (Gbrowse, Mauve and custom views) to facilitate genome comparisons. A choice of simple and more flexible user-friendly Boolean search features allows researchers to search and compare annotations or sequences within or between genomes. Other features include more accurate protein subcellular localization predictions and a user-friendly, Boolean searchable log file of updates for the reference strain PAO1. This database aims to continue to provide a high quality, annotated genome resource for the research community and is available under an open source license. | 18,978,025 |
Targeted delivery of cisplatin to prostate cancer cells by aptamer functionalized Pt(IV) prodrug-PLGA-PEG nanoparticles. | Cisplatin is used to treat a variety of tumors, but dose limiting toxicities or intrinsic and acquired resistance limit its application in many types of cancer including prostate. We report a unique strategy to deliver cisplatin to prostate cancer cells by constructing Pt(IV)-encapsulated prostate-specific membrane antigen (PSMA) targeted nanoparticles (NPs) of poly(D,L-lactic-co-glycolic acid) (PLGA)-poly(ethylene glycol) (PEG)-functionalized controlled release polymers. By using PLGA-b-PEG nanoparticles with PSMA targeting aptamers (Apt) on the surface as a vehicle for the platinum(IV) compound c,t,c-[Pt(NH(3))(2)(O(2)CCH(2)CH(2)CH(2)CH(2)CH(3))(2)Cl(2)] (1), a lethal dose of cisplatin was delivered specifically to prostate cancer cells. PSMA aptamer targeted delivery of Pt(IV) cargos to PSMA(+) LNCaP prostate cancer cells by endocytosis of the nanoparticle vehicles was demonstrated using fluorescence microscopy by colocalization of green fluorescent labeled cholesterol-encapsulated NPs and early endosome marker EEA-1. The choice of linear hexyl chains in 1 was the result of a systematic study to optimize encapsulation and controlled release from the polymer without compromising either feature. Release of cisplatin from the polymeric nanoparticles after reduction of 1 and formation of cisplatin 1,2-intrastrand d(GpG) cross-links on nuclear DNA was confirmed by using a monoclonal antibody for the adduct. A comparison between the cytotoxic activities of Pt(IV)-encapsulated PLGA-b-PEG NPs with the PSMA aptamer on the surface (Pt-NP-Apt), cisplatin, and the nontargeted Pt(IV)-encapsulated NPs (Pt-NP) against human prostate PSMA-overexpressing LNCaP and PSMA(-) PC3 cancer cells revealed significant differences. The effectiveness of PSMA targeted Pt-NP-Apt nanoparticles against the PSMA(+) LNCaP cells is approximately an order of magnitude greater than that of free cisplatin. | 18,978,032 |
The action of high K+ and aglycaemia on the electrical properties and synaptic transmission in rat intracardiac ganglion neurones in vitro. | We have investigated the action of two elements of acute ischaemia, high potassium and aglycaemia, on the electrophysiological properties and ganglionic transmission of adult rat intracardiac ganglion (ICG) neurones. We used a whole-mount ganglion preparation of the right atrial ganglion plexus and sharp microelectrode recording techniques. Increasing extracellular K(+) from its normal value of 4.7 mm to 10 mm decreased membrane potential and action potential after-hyperpolarization amplitude but otherwise had no effect on postganglionic membrane properties. It did, however, reduce the ability of synaptically evoked action potentials to follow high-frequency (100 Hz) repetitive stimulation. A further increase in K(+) changed both the passive and the active membrane properties of the postganglionic neurone: time constant, membrane resistance and action potential overshoot were all decreased in high K(+) (20 mm). The ICG neurones display a predominantly phasic discharge in response to prolonged depolarizing current pulses. High K(+) had no impact on this behaviour but reduced the time-dependent rectification response to hyperpolarizing currents. At 20 mm, K(+) practically blocked ganglionic transmission in most neurones at all frequencies tested. Aglycaemia, nominally glucose-free physiological saline solution (PSS), increased the time constant and membrane resistance of ICG neurones but otherwise had no action on their passive or active properties or ganglionic transmission. However, the combination of aglycaemia and 20 mm K(+) displayed an improvement in passive properties and ganglionic transmission when compared with 20 mm K(+) PSS. These data indicate that the presynaptic terminal is the primary target of high extracellular potassium and that aglycaemia may have protective actions against this challenge. | 18,978,036 |
The pH-responsive regulon of HP0244 (FlgS), the cytoplasmic histidine kinase of Helicobacter pylori. | Helicobacter pylori colonizes the acidic gastric environment, in contrast to all other neutralophiles, whose acid resistance and tolerance responses allow only gastric transit. This acid adaptation is dependent on regulation of gene expression in response to pH changes in the periplasm and cytoplasm. The cytoplasmic histidine kinase, HP0244, which until now was thought only to regulate flagellar gene expression via its cognate response regulator, HP0703, was found to generate a response to declining medium pH. Although not required for survival at pH 4.5, HP0244 is required for survival at pH 2.5 with 10 mM urea after 30 min. Transcriptional profiling of a HP0244 deletion mutant grown at pH 7.4 confirmed the contribution of HP0244 to sigma(54) activation via HP0703 to coordinate flagellar biosynthesis by a pH-independent regulon that includes 14 flagellar genes. Microarray analysis of cells grown at pH 4.5 without urea revealed an additional 22 genes, including 4 acid acclimation genes (ureA, ureB, ureI, and amiE) that are positively regulated by HP0244. Additionally, 86 differentially expressed genes, including 3 acid acclimation genes (ureF, rocF [arginase], and ansB [asparaginase]), were found in cells grown at pH 2.5 with 30 mM urea. Hence, HP0244 has, in addition to the pH-independent flagellar regulon, a pH-dependent regulon, which allows adaptation to a wider range of environmental acid conditions. An acid survival study using an HP0703 mutant and an electrophoretic mobility shift assay with in vitro-phosphorylated HP0703 showed that HP0703 does not contribute to acid survival and does not bind to the promoter regions of several genes in the HP0244 pH-dependent regulon, suggesting that there is a pathway outside the HP0703 regulon which transduces the acid-responsive signal sensed by HP0244. | 18,978,046 |
Improved thermostability and acetic acid tolerance of Escherichia coli via directed evolution of homoserine o-succinyltransferase. | In Escherichia coli, growth is limited at elevated temperatures mainly because of the instability of a single enzyme, homoserine o-succinyltransferase (MetA), the first enzyme in the methionine biosynthesis pathway. The metA gene from the thermophile Geobacillus kaustophilus cloned into the E. coli chromosome was found to enhance the growth of the host strain at elevated temperature (44 degrees C), thus confirming the limited growth of E. coli due to MetA instability. In order to improve E. coli growth at higher temperatures, we used random mutagenesis to obtain a thermostable MetA(E. coli) protein. Sequencing of the thermotolerant mutant showed five amino acid substitutions: S61T, E213V, I229T, N267D, and N271K. An E. coli strain with the mutated metA gene chromosomally inserted showed accelerated growth over a temperature range of 34 to 44 degrees C. We used the site-directed metA mutants to identify two amino acid residues responsible for the sensitivity of MetA(E. coli) to both heat and acids. Replacement of isoleucine 229 with threonine and asparagine 267 with aspartic acid stabilized the protein. The thermostable MetA(E. coli) enzymes showed less aggregation in vivo at higher temperature, as well as upon acetic acid treatment. The data presented here are the first to show improved E. coli growth at higher temperatures solely due to MetA stabilization and provide new knowledge for designing E. coli strains that grow at higher temperatures, thus reducing the cooling cost of bioprocesses. | 18,978,085 |
Effect of diaphragm and lubricant gel provision on human papillomavirus infection among women provided with condoms: a randomized controlled trial. | To estimate the effect of providing women with a latex diaphragm, lubricant gel, and male condoms (intervention) compared with condoms alone (control) on human papillomavirus (HPV) incidence and clearance. Participants were 2,040 human immunodeficiency virus (HIV)-negative Zimbabwean women enrolled in a randomized trial estimating the effect of the intervention on HIV acquisition. Clinicians collected cervical samples for HPV testing at baseline, 12 months, and exit. L1 consensus polymerase chain reaction primers were used to determine HPV presence and type. We found no differences in the following outcomes: HPV prevalence at the time of the first postenrollment HPV test (intention-to-treat analysis, relative risk [RR] 1.02, 95% confidence interval [CI] 0.90-1.16); HPV incidence at 12 months among women HPV-negative at baseline (RR 0.95, 95% CI 0.80-1.14); and HPV clearance at 12 months among women HPV-positive at baseline (RR 0.80, 95% CI 0.61-1.05). Clearance of HPV type 58 was lower in the intervention group at 12 months (RR 0.67, 95% CI 0.48-0.92), but not at exit (RR 0.93, 95% CI 0.75-1.16); clearance of HPV type 18 was lower in the intervention group at exit (RR 0.55, 95% CI 0.33-0.89), but not at 12 months (RR 0.55, 95% CI 0.29-1.05). Women reporting diaphragm/gel use at 100% of prior sex acts had a lower likelihood of having one or more new HPV types detected at 12 months (RR 0.75, 95% CI 0.58-0.96) and exit (RR 0.77, 95% CI 0.59-0.99). Among women receiving risk reduction counseling and condoms in an HIV prevention program, diaphragm plus lubricant gel provision did not affect HPV incidence or clearance. ClinicalTrials.gov, www.clinicaltrials.gov, NCT00121459 I. | 18,978,097 |
Cigarette smoking, androgen levels, and hot flushes in midlife women. | To test the hypothesis that cigarette smoking is associated with hot flushes through a mechanism involving androgen levels, progesterone levels, sex hormone-binding globulin levels, or the ratio of androgens to estrogens. Women with and without hot flushes were recruited from Baltimore, Maryland, and the surrounding counties. Women were between 45 and 54 years of age, with at least three menstrual periods in the previous 12 months, and were not postmenopausal. Study participants completed a questionnaire and gave a blood sample for hormone measurements. Current smokers had significantly higher androstenedione levels and a higher androgen-to-estrogen ratio than never smokers. Current smokers had significantly lower progesterone levels compared with never smokers. Former and current cigarette smokers had increased odds of experiencing hot flushes compared with never smokers (former: odds ratio [OR] 1.41, 95% confidence interval [CI] 0.99-2.01; current: OR 2.43, 95% CI 1.28-4.62). This association, however, was not attenuated by the addition of hormones to the smoking and hot-flush model. Cigarette smoking is associated with hot flushes through a mechanism that may not involve alterations in hormone levels or their ratios. II. | 18,978,103 |
Effective treatment of vaginal atrophy with an ultra-low-dose estradiol vaginal tablet. | To evaluate the efficacy of ultra-low-dose 10-microgram 17beta-estradiol (E2) vaginal tablets for treatment of vaginal atrophy. Postmenopausal women (N=309) were randomly assigned to 10-microgram E2 or placebo vaginal tablets for 52 weeks in a multicenter, double-blind study. Primary efficacy endpoints included change from baseline to week 12 in vaginal cytology, vaginal pH, and most bothersome urogenital symptoms score. Grading of vaginal health was a secondary efficacy assessment. Safety assessments included endometrial biopsy, physical and gynecologic examinations, and recording adverse events. At week 12, the change from baseline for 10 micrograms E2 compared with placebo demonstrated significant improvement in vaginal Maturation Index (proportion of parabasal cells: -37% compared with -9%; superficial cells: 13% compared with 4%; intermediate cells: 24% compared with 5%; P<.001 for each), Maturation Value (25.0 compared with 6.5, P<.001), grading of vaginal health (-0.91 compared with -0.51, P<.001), vaginal pH grade (-1.3 compared with -0.4, P<.001), and most bothersome symptoms score (-1.23 compared with -0.87, P=.003). For each component of vaginal Maturation Index, vaginal Maturation Value, grading of vaginal health, and vaginal pH, treatment effects were statistically different from placebo after 2 weeks of treatment. For most bothersome symptoms, treatment effect became apparent after 4 weeks and reached statistical significance at week 8 of therapy. All treatment effects were statistically significant at week 52. There were no major safety findings regarding physical, gynecologic, or laboratory assessments. After 12 weeks of treatment, an ultra-low-dose 10-microgram E2 vaginal tablet, compared with placebo, demonstrated significant improvement for the primary endpoints: vaginal cytology and pH and most bothersome urogenital symptoms score. ClinicalTrials.gov, http://clinicaltrials.gov, NCT00108849 I. | 18,978,105 |
A protocol of dual prophylaxis for venous thromboembolism prevention in gynecologic cancer patients. | To evaluate a quality improvement protocol for venous thromboembolism prevention in postoperative gynecologic cancer patients. On January 1, 2006, we initiated a universal protocol of dual prophylaxis with sequential compression devices and three times daily heparin (or daily low molecular weight heparin) until discharge in gynecologic cancer patients having major surgery. Patients with both malignancy and age over 60 years (or history of prior clot) were discharged on 2 weeks of anticoagulant. Before January 2006, all patients were given sequential compression devices starting before the induction of anesthesia, continuing until discharge from the hospital. Records of gynecologic cancer service patients admitted in 2005 and 2006 were reviewed, excluding patients with a history of heparin-induced thrombocytopenia or those admitted on an anticoagulant. Any pulmonary embolism or deep vein thrombosis diagnosed within 6 weeks of surgery was identified. We performed chi2 and Wilcoxon rank sum tests as well as multivariable regression analysis for confounders. Six of the 311 women meeting inclusion criteria in 2006 (1.9%) and 19 of 294 (6.5%) in 2005 had venous thromboembolism (odds ratio 0.33, 95% confidence interval 0.12-0.88, multivariable analysis adjusting for baseline differences between the groups). Heparin was given to 98.1% of patients in the hospital in 2006, and 91.1% of those meeting high-risk criteria were discharged on an anticoagulant. No differences in major bleeding complications were seen between years. A protocol of dual prophylaxis with prolonged prophylaxis in high-risk patients was successfully implemented and was associated with a significant reduction in the rate of venous thromboembolism without increasing bleeding complications. II. | 18,978,110 |
Activation of the fibrinolytic cascade early in pregnancy among women with spontaneous preterm birth. | To evaluate the association of early pregnancy concentrations of thrombin-antithrombin III complex with subsequent spontaneous preterm birth. In a nested case-control study, thrombin-antithrombin III complex was measured in plasma before 20 weeks of gestation (mean 9.9 weeks) among women without chronic conditions, preeclampsia, or growth restriction. C-reactive protein and non-high-density lipoprotein cholesterol were also measured. Women with spontaneous preterm birth before 34 weeks of gestation (n=29) and 34 weeks to 36 weeks of gestation (n=72) were compared with women with term births occurring at or after 37 weeks (n=219). Polychotomous logistic regression was used to relate elevated thrombin-antithrombin III complex (greater than 5.5 ng/mL), dyslipidemia (non-high-density lipoprotein cholesterol greater than the 90th percentile), and inflammation (C-reactive protein at or above 8 micrograms/mL) to risk of spontaneous preterm birth subtypes. Women with spontaneous preterm birth compared with term births had elevated thrombin-antithrombin III complex (P=.02), and they were more likely to have a thrombin-antithrombin III complex greater than 5.5 ng/mL (P<.01). Women with thrombin-antithrombin III complex in the highest compared with lowest quartile had a 4.6-fold (95% confidence interval 1.3-15.8) increased risk for spontaneous preterm birth before 34 weeks of gestation, adjusted for body mass index, race, inflammation, dyslipidemia, and gestational age at sampling. There was a dose-response trend between thrombin-antithrombin III complex and spontaneous preterm birth before 34 weeks (P<.01) and 34 to 36 weeks (P=.03). There is evidence of early pregnancy systemic fibrinolysis among women with spontaneous preterm birth before 34 weeks of gestation independent of inflammation and dyslipidemia, perhaps secondary to microvascular injury. II. | 18,978,114 |
Lung cancer gene associated with COPD: triple whammy or possible confounding effect? | Recently, several large genome-wide association studies have identified a putative "lung cancer" locus in the nicotinic acetylcholine receptor subunit genes (nAChR) on 15q25. However, these findings may be confounded by the presence of chronic obstructive pulmonary disease (COPD), which is also strongly associated with smoking exposure and lung cancer. This is likely as the prevalence of COPD in lung cancer cohorts is as much as two-fold greater than that reported in smoking control populations (50 versus 20%). The present authors compared the genotype frequencies of the most strongly associated single nucleotide polymorphism (rs16969968) in the alpha5 subunit of the nAChR gene cluster between three matched smoking cohorts. The AA genotype was found to be more frequent and was seen in 437 (16%) lung cancer cases and 445 (14%) COPD cases compared with 475 (9%) healthy smoking controls. More importantly, when 429 lung cancer cases were divided according to spirometry results (performed within 3 months of diagnosis, prior to surgery and in the absence of effusions or collapse), the AA genotype was present in 19 and 11% of cases with and without COPD, respectively. These findings suggest that the association between the alpha5 subunit nicotinic acetylcholine receptor single nucleotide polymorphism and lung cancer may, in part, be confounded by chronic obstructive pulmonary disease. | 18,978,134 |
Cell kinetics and gene expression changes in colorectal cancer patients given resistant starch: a randomised controlled trial. | This study investigated the effects of oral supplementation of resistant starch (RS) on tumour cell and colonic mucosal cell kinetics and on gene expression in patients with colorectal cancer (CRC), and its potential role in colon cancer prevention. 65 patients with CRC were randomised to treatment with RS or ordinary starch (OS) and were given starch treatment for up to 4 weeks. Pretreatment and post-treatment biopsies were obtained from the tumour and colonic mucosa, and the effects of the starch treatment on cell proliferation and expression of the cell cycle regulatory genes CDK4 (cyclin-dependent kinase 4) and GADD45A (growth arrest and DNA damage-inducible, alpha) were investigated. The proportion of mitotic cells in the top half of the colonic crypt was significantly lower following RS treatment (3.1 (1.5), mean (SEM)) as compared with OS treatment (13.7 (3.2)) (p = 0.028). However, there was no effect of RS treatment on crypt dimensions and tumour cell proliferation index. There was significant upregulation in expression of CDK4 (p<0.01) and downregulation in expression of GADD45A (p<0.001) in the tumour tissue when compared with macroscopically normal mucosa. Following RS treatment, CDK4 expression in tumours (0.88 (0.15)) was twofold higher than that in the OS group (0.37 (0.16)) (p = 0.02). The expression of GADD45A, which was downregulated in the presence of cancer, was significantly upregulated (p = 0.048) following RS treatment (1.41 (0.26)) as compared with OS treatment (0.56 (0.3)). However, there were no significant differences in the expression of these genes in the normal mucosa following starch treatment. Cell proliferation in the upper part of colonic crypts is a premalignant marker and its reduction by RS supplementation is consistent with an antineoplastic action of this food component. Differential expression of the key cell cycle regulatory genes may contribute to the molecular mechanisms underlying these antineoplastic effects of RS. | 18,978,177 |
Vascular endothelial growth factor and angiopoietin-2 play a major role in the pathogenesis of vascular leakage in cirrhotic rats. | The extent and molecular mechanisms governing plasma extravasation and formation of ascites in cirrhosis are unknown. Vascular endothelial growth factor-A (VEGF-A) and angiopoietin-2 (Ang-2) are endogenous substances with powerful vascular permeability effects. We assessed regional blood flow, vascular leakage, mRNA and tissular expression of VEGF-A and Ang-2 and vascular permeability following VEGF receptor 2 blockade in control and cirrhotic rats to define the vascular territories showing altered vascular permeability in cirrhosis and to determine whether VEGF-A and Ang-2 are involved in this phenomenon. Arterial blood flow was analysed with the coloured microsphere method. Vascular leakage was measured and visualised with the dye Evan's Blue and colloidal carbon techniques, respectively. VEGF-A and Ang-2 expression were determined by real-time polymerase chain reaction (RT-PCR), immunohistochemistry and western blot. The effect on vascular permeability induced by VEGFR(2) blockade was assessed by administration of the receptor inhibitor SU11248. Arterial blood flow was increased in the mesentery, pancreas and small intestine but not in the kidney and spleen of cirrhotic rats as compared to controls. Increased vascular leakage was observed in the mesentery and liver, where colloidal carbon spread from microvessels to the adjacent fibrotic tracts. Increased hepatic and mesenteric expression of VEGF-A and Ang-2 was found in cirrhotic rats as compared to controls. Blockade of VEGFR(2) markedly reduced hepatic and mesenteric vascular leakage in cirrhotic rats. Enhanced endothelial permeability is restricted to the hepatic and mesenteric vascular beds in cirrhotic rats with ascites and VEGF-A and Ang-2 are key factors in the signalling pathways regulating this dysfunction. | 18,978,178 |
A therapeutic dose of doxorubicin activates ubiquitin-proteasome system-mediated proteolysis by acting on both the ubiquitination apparatus and proteasome. | The ubiquitin proteasome system (UPS) degrades abnormal proteins and most unneeded normal proteins, thereby playing a critical role in protein homeostasis in the cell. Proteasome inhibition is effective in treating certain forms of cancer, while UPS dysfunction is increasingly implicated in the pathogenesis of many severe and yet common diseases. It has been previously shown that doxorubicin (Dox) enhances the degradation of a UPS surrogate substrate in mouse hearts. To address the underlying mechanism, in the present study, we report that 1) Dox not only enhances the degradation of an exogenous UPS reporter (GFPu) but also antagonizes the proteasome inhibitor-induced accumulation of endogenous substrates (e.g., beta-catenin and c-Jun) of the UPS in cultured NIH 3T3 cells and cardiomyocytes; 2) Dox facilitates the in vitro degradation of GFPu and c-Jun by the reconstituted UPS via the enhancement of proteasomal function; 3) Dox at a therapeutically relevant dose directly stimulates the peptidase activities of purified 20S proteasomes; and 4) Dox increases, whereas proteasome inhibition decreases, E3 ligase COOH-terminus of heat shock protein cognate 70 in 3T3 cells via a posttranscriptional mechanism. These new findings suggest that Dox activates the UPS by acting directly on both the ubiquitination apparatus and proteasome. | 18,978,187 |
Impact of diet and stress on the development of preeclampsia-like symptoms in p57kip2 mice. | The cyclin-dependent kinase inhibitor p57(kip2) regulates the cell cycle of trophoblastic cells. It has been established by a Japanese group that the heterozygous p57(kip2) knockout (p57(-/+)) mice are a good model of preeclampsia as they develop hypertension, proteinuria, and placental pathology. However, apart from the placental pathology, we could not observe these symptoms in our laboratory. Hence, we investigated the impact of diet and stress on this model. To do so, we compared the effects of the Japanese diet to that of the North American diet used by our animal facility. Furthermore, the impact of stress was determined by placing the mice in a restraining device before and at the end of gestation. Although the Japanese diet did not have any impact on blood pressure or proteinuria, the mice did develop endothelial dysfunction, left ventricular hypertrophy, as well as increased placental pathology. Also, all mice had smaller litters when fed the Japanese diet. However, stress response of these mice was not increased during gestation; in fact, a decrease was observed in the p57(-/+) mice, suggesting that this was probably not a player in the development of the pathology. Taken together, these results suggest that other environmental factors may have been implicated in the development of preeclampsia-like symptoms in this animal model. Moreover, we demonstrated that placental pathology and genetic factors are not sufficient to trigger preeclampsia-like symptoms in this model and that the diet might play an important part in the development of this multifactorial disease. | 18,978,188 |
A short duration of high-fat diet induces insulin resistance and predisposes to adverse left ventricular remodeling after pressure overload. | Insulin resistance is an increasingly prevalent condition in humans that frequently clusters with disorders characterized by left ventricular (LV) pressure overload, such as systemic hypertension. To investigate the impact of insulin resistance on LV remodeling and functional response to pressure overload, C57BL6 male mice were fed a high-fat (HFD) or a standard diet (SD) for 9 days and then underwent transverse aortic constriction (TAC). LV size and function were assessed in SD- and HFD-fed mice using serial echocardiography before and 7, 21, and 28 days after TAC. Serial echocardiography was also performed on nonoperated SD- and HFD-fed mice over a period of 6 wk. LV perfusion was assessed before and 7 and 28 days after TAC. Nine days of HFD induced systemic and myocardial insulin resistance (assessed by myocardial 18F-fluorodeoxyglucose uptake), and myocardial perfusion response to acetylcholine was impaired. High-fat feeding for 28 days did not change LV size and function in nonbanded mice; however, TAC induced greater hypertrophy, more marked LV systolic and diastolic dysfunction, and decreased survival in HFD-fed compared with SD-fed mice. Compared with SD-fed mice, myocardial perfusion reserve was decreased 7 days after TAC, and capillary density was decreased 28 days after TAC in HFD-fed mice. A short duration of HFD induces insulin resistance in mice. These metabolic changes are accompanied by increased LV remodeling and dysfunction after TAC, highlighting the impact of insulin resistance in the development of pressure-overload-induced heart failure. | 18,978,196 |
Mechanism and rate of glucose absorption differ between an Australian honeyeater (Meliphagidae) and a lorikeet (Loriidae). | Efficient mechanisms of glucose absorption are necessary for volant animals as a means of reducing mass during flight: they speed up gut transit time and require smaller volume and mass of gut tissue. One mechanism that may be important is absorption via paracellular (non-mediated) pathways. This may be particularly true for nectarivorous species which encounter large quantities of sugar in their natural diet. We investigated the extent of mediated and non-mediated glucose absorption in red wattlebirds Anthochaera carunculata (Meliphagidae) and rainbow lorikeets Trichoglossus haematodus (Loriidae) to test the hypothesis that paracellular uptake accounts for a significant proportion of total glucose uptake in these species. We found that routes of glucose absorption are highly dynamic in both species. In lorikeets, absorption of L-glucose (non-mediated uptake) is slower than that of D-glucose (mediated and non-mediated uptake), with as little as 10% of total glucose absorbed by the paracellular pathway initially (contrasting previous indirect estimates of approximately 80%). Over time, however, more glucose may be absorbed via the paracellular route. Glucose absorption by both mediated and non-mediated mechanisms in wattlebirds occurred at a faster rate than in lorikeets, and wattlebirds also rely substantially on paracellular uptake. In wattlebirds, we recorded higher bioavailability of L-glucose (96+/-3%) compared with D-glucose (57+/-2%), suggesting problems with the in vivo use of radiolabeled d-glucose. Further trials with 3-O-methyl-D-glucose revealed high bioavailability in wattlebirds (90+/-5%). This non-metabolisable glucose analogue remains the probe of choice for measuring uptake rates in vivo, especially in birds in which absorption and metabolism occur extremely rapidly. | 18,978,218 |
A microarray-based transcriptomic time-course of hyper- and hypo-osmotic stress signaling events in the euryhaline fish Gillichthys mirabilis: osmosensors to effectors. | Cells respond to changes in osmolality with compensatory adaptations that re-establish ion homeostasis and repair disturbed aspects of cell structure and function. These physiological processes are highly complex, and require the coordinated activities of osmosensing, signal transducing and effector molecules. Although the critical role of effector proteins such as Na+, K+-ATPases and Na+/K+/Cl(-) co-transporters during osmotic stress are well established, comparatively little information is available regarding the identity or expression of the osmosensing and signal transduction genes that may govern their activities. To better resolve this issue, a cDNA microarray consisting of 9207 cDNA clones was used to monitor gene expression changes in the gill of the euryhaline fish Gillichthys mirabilis exposed to hyper- and hypo-osmotic stress. We successfully annotated 168 transcripts differentially expressed during the first 12 h of osmotic stress exposure. Functional classifications of genes encoding these transcripts reveal that a variety of biological processes are affected. However, genes participating in cell signaling events were the dominant class of genes differentially expressed during both hyper- and hypo-osmotic stress. Many of these genes have had no previously reported role in osmotic stress adaptation. Subsequent analyses used the novel expression patterns generated in this study to place genes within the context of osmotic stress sensing, signaling and effector events. Our data indicate multiple major signaling pathways work in concert to modify diverse effectors, and that these molecules operate within a framework of regulatory proteins. | 18,978,229 |
Pre-operative predictors of the length of hospital stay in total knee replacement. | In Scotland, the number of primary total knee replacements performed annually has been increasing steadily. The price of the implant is fixed but the length of hospital stay is variable. We prospectively investigated all patients who underwent primary unilateral total knee replacement in the Scottish region of Fife, between December 1994 and February 2007 and assessed their recorded pre-operative details. The data were analysed using univariate and multiple linear regression statistical analysis. Data on the length of stay were available from a total of 2106 unilateral total knee replacements. The median length of hospital stay was eight days. The significant pre-operative risk factors for an increased length of stay were the year of admission, details of the consultant looking after the patient, the stair score, the walking-aid score and age. Awareness of the pre-operative factors which increase the length of hospital stay may provide the opportunity to influence them favourably and to reduce the time in hospital and the associated costs of unilateral total knee replacement. | 18,978,261 |
The epidemiology of fractures in adolescents with reference to social deprivation. | A relationship between social deprivation and the incidence of fracture in adolescents has not previously been shown. We have used a complete fracture database to identify adolescents who sustained fractures in 2000. The 2001 Scottish census was used to obtain age-specific population and deprivation data according to the Carstairs score. Regression analysis determined the relationship between the incidence of fractures and social deprivation. We analysed 1574 adolescents with fractures (1083 male, 491 female). The incidence of fractures in this group was 21.8 per thousand (31.0 male, 13.1 female). Social deprivation predicted the incidence in adolescent males and females. The incidence of fractures of the proximal upper limb and distal radius in females was overwhelmingly influenced by socioeconomic factors. Males of 15 to 20 years of age were more likely to sustain fractures of the hand and carpus if they lived in economically depressed neighbourhoods. | 18,978,270 |
Hepatocarcinogenic susceptibility of fenofibrate and its possible mechanism of carcinogenicity in a two-stage hepatocarcinogenesis model of rasH2 mice. | Fenofibrate (FF) has previously been shown to induce hepatocellular neoplasia in a conventional mouse bioassay (NDA 1993), but there has been no report to examine the carcinogenic susceptibility of rasH2 mice to this chemical. In the present study, male rasH2 mice were subjected to a two-thirds partial hepatectomy (PH), followed by an N-diethylnitrosamine (DEN) initiation twenty-four hours after PH, and given a diet containing 0, 1200, or 2400 ppm FF for seven weeks. The incidences of preneoplastic foci were significantly increased in mice from the FF-treated groups. Immunohistochemistry revealed that significant increases in proliferating cell nuclear antigen (PCNA)-positive cells and cytokeratin 8/18 positive foci were observed in FF-treated groups. In addition, the transgene and several downstream molecules such as c-myc, c-jun, activating transcription factor 3 (ATF3), and cyclin D1 were overexpressed in these groups. These results suggest that the hepatocarcinogenic activity of rasH2 mice to FF can be detected in this hepatocarcinogenesis model and that up-regulation of genes for the ras/MAPK pathway and cell cycle was probably involved in the hepatocarcinogenic mechanism of rasH2 mice. | 18,978,307 |
Involving patients in decisions during psychiatric consultations. | Patient involvement in the decision-making process is a key element for good clinical practice. Few data are available on patient involvement in psychiatry. To assess in a psychiatric out-patient context how psychiatrists involve patients in therapeutic decisions and to determine the extent to which patient and psychiatrist characteristics contribute to patient involvement. Eighty transcripts from audiotaped first out-patient consultations, conducted by 16 psychiatrists, were rated with the OPTION (observing patient involvement) scale. Interrater reliability indices were obtained for 30 randomly selected interviews. Associations between OPTION scores and some clinical and socio-demographic variables were tested using t-test, ANOVA and Pearson's correlation coefficient where appropriate. The distribution of scores for each psychiatrist was assessed by intracluster correlation coefficients. Interrater reliability and internal consistency of the OPTION scale in the psychiatric setting were satisfactory. The total score and the ratings for the single OPTION items showed a skewed distribution, with a prevalence of scores in the low range of abilities, corresponding to minimal attempts to involve patients or a minimal skill level. The OPTION scale proves to be a reliable instrument to assess patient involvement in a psychiatric setting. Psychiatrists showed poor patient involvement abilities parallel to previous findings in psychiatry and primary care. They need to be encouraged to share treatment decisions with their patients and to apply patient involvement skills. Further research is needed to establish which patient variables and clinical settings in psychiatry are more amenable to shared decisions, and how participation of psychiatric patients in treatment decisions will affect the outcome. | 18,978,325 |
Effects of perinatal PBDE exposure on hepatic phase I, phase II, phase III, and deiodinase 1 gene expression involved in thyroid hormone metabolism in male rat pups. | Previous studies demonstrated that perinatal exposure to polybrominated diphenyl ethers (PBDEs), a major class of brominated flame retardants, may affect thyroid hormone (TH) concentrations by inducing hepatic uridinediphosphate-glucoronosyltransferases (UGTs). This study further examines effects of the commercial penta mixture, DE-71, on genes related to TH metabolism at different developmental time points in male rats. DE-71 is predominately composed of PBDE congeners 47, 99, 100, 153, 154 with low levels of brominated dioxin and dibenzofuran contaminants. Pregnant Long-Evans rats were orally administered 1.7 (low), 10.2 (mid), or 30.6 (high) mg/kg/day of DE-71 in corn oil from gestational day (GD) 6 to postnatal day (PND) 21. Serum and liver were collected from male pups at PND 4, 21, and 60. Total serum thyroxine (T(4)) decreased to 57% (mid) and 51% (high) on PND 4, and 46% (mid) dose and 25% (high) on PND 21. Cyp1a1, Cyp2b1/2, and Cyp3a1 enzyme and mRNA expression, regulated by aryl hydrocarbon receptor, constitutive androstane receptor, and pregnane xenobiotic receptor, respectively, increased in a dose-dependent manner. UGT-T(4) enzymatic activity significantly increased, whereas age and dose-dependent effects were observed for Ugt1a6, 1a7, and 2b mRNA. Sult1b1 mRNA expression increased, whereas that of transthyretin (Ttr) decreased as did both the deiodinase I (D1) enzyme activity and mRNA expression. Hepatic efflux transporters Mdr1 (multidrug resistance), Mrp2 (multidrug resistance-associated protein), and Mrp3 and influx transporter Oatp1a4 mRNA expression increased. In this study the most sensitive responses to PBDEs following DE-71 exposure were CYP2B and D1 activities and Cyb2b1/2, d1, Mdr1, Mrp2, and Mrp3 gene expression. All responses were reversible by PND 60. In conclusion, deiodination, active transport, and sulfation, in addition to glucuronidation, may be involved in disruption of TH homeostasis due to perinatal exposure to DE-71 in male rat offspring. | 18,978,342 |
A phase I study of periocular topotecan in children with intraocular retinoblastoma. | To identify the maximum tolerated dose and dose-limiting toxicity of periocular topotecan in patients with relapsed or resistant intraocular retinoblastoma who are facing imminent enucleation. For this phase I study, a starting dose of 0.5 mg of periocular topotecan administered through a 25-gauge needle was given with intrapatient escalation at a rate of 0.5 mg/cycle according to toxicity, up to a maximum dose of 2 mg. Two courses separated by 2 weeks were scheduled. Plasma levels of topotecan were measured by high-performance liquid chromatography in patients with available intravenous catheters. Seven eyes of five patients were treated with a total of 14 courses of periocular topotecan. Only mild orbital edema occurred, and grade 1 vomiting developed in the first patient that was controlled with ondansetron for the following courses. Dose-limiting toxicity was not reached and the maximum tolerated dose was set at the target dose of 2 mg (n=5 eyes). Lactone topotecan systemic exposure was lower than 55 ng/mL x h and it correlated linearly with dose in this small cohort. Even though the study was not designed to assess response, one eye was preserved after a partial response, but the remaining six were enucleated, either after a short period of disease stabilization followed by further therapy with other agents in five patients or by rapidly progressive disease in one. The dose limiting toxicity was not reached. Up to 2 mg of periocular topotecan could be given safely, but further studies are necessary to determine its effect on retinoblastoma (ClinicalTrials.gov number, NCT00460876). | 18,978,345 |
Evf, a virulence factor produced by the Drosophila pathogen Erwinia carotovora, is an S-palmitoylated protein with a new fold that binds to lipid vesicles. | Erwinia carotovora are phytopathogenic Gram-negative bacteria of agronomic interest as these bacteria are responsible for fruit soft rot and use insects as dissemination vectors. The Erwinia carotovora carotovora strain 15 (Ecc15) is capable of persisting in the Drosophila gut by the sole action of one protein, Erwinia virulence factor (Evf). However, the precise function of Evf is elusive, and its sequence does not provide any indication as to its biochemical function. We have solved the 2.0-angstroms crystal structure of Evf and found a protein with a complex topology and a novel fold. The structure of Evf confirms that Evf is unlike any virulence factors known to date. Most remarkably, we identified palmitoic acid covalently bound to the totally conserved Cys209, which provides important clues as to the function of Evf. Mutation of the palmitoic binding cysteine leads to a loss of virulence, proving that palmitoylation is at the heart of Evf infectivity and may be a membrane anchoring signal. Fluorescence studies of the sole tryptophan residue (Trp94) demonstrated that Evf was indeed able to bind to model membranes containing negatively charged phospholipids and to promote their aggregation. | 18,978,353 |
FANCJ is a structure-specific DNA helicase associated with the maintenance of genomic G/C tracts. | Fanconi anemia (FA) is a heritable human cancer-susceptibility disorder, delineating a genetically heterogenous pathway for the repair of replication-blocking lesions such as interstrand DNA cross-links. Here we demonstrate that one component of this pathway, FANCJ, is a structure-specific DNA helicase that dissociates guanine quadruplex DNA (G4 DNA) in vitro. Moreover, in contrast with previously identified G4 DNA helicases, such as the Bloom's helicase (BLM), FANCJ unwinds G4 substrates with 5'-3' polarity. In the FA-J human patient cell line EUFA0030 the loss of FANCJ G4 unwinding function correlates with the accumulation of large genomic deletions in the vicinity of sequences, which match the G4 DNA signature. Together these findings support a role for FANCJ in the maintenance of potentially unstable genomic G/C tracts during replication. | 18,978,354 |
Immune function effects of dental amalgam in children: a randomized clinical trial. | Dental amalgam is a widely used restorative material containing 50 percent elemental mercury that emits mercury vapor. No randomized clinical trials have determined whether there are adverse immunological effects associated with this low-level mercury exposure in children. The objective of this study was to evaluate a subpopulation of the participants in the New England Children's Amalgam Trial for in vitro manifestations of immunotoxic effects of dental amalgam. The authors conducted a randomized clinical trial in which children requiring dental restorative treatment were randomly assigned to receive either amalgam for posterior restorations or resin-based composite restorations. They assessed 66 children, aged 6 to 10 years, for total white blood cell counts, specific lymphocyte (T-cell and B-cell) counts and lymphocyte, neutrophil and monocyte responsiveness across a five-year period. Because of the small number of participants, the authors acknowledge that the study is exploratory in nature and has limited statistical power. The mean number of tooth surfaces restored during the five-year period was 7.8 for the amalgam group and 10.1 for the composite group. In the amalgam group, there was a slight, but not statistically significant, decline in responsiveness of T cells and monocytes at five to seven days after treatment; the authors consistently observed no differences at six, 12 or 60 months. The findings of this study confirm that treatment of children with amalgam restorations leads to increased, albeit low-level, exposure to mercury. In this exploratory analysis of immune function, amalgam exposure did not cause overt immune deficits, although small transient effects were observed five to seven days after restoration placement. These findings suggest that immunotoxic effects of amalgam restorations are minimal and transient in children and most likely do not need to be of concern to practitioners considering the use of this restorative dental material. | 18,978,388 |
A comparison of two nonoperative methods of idiopathic clubfoot correction: the Ponseti method and the French functional (physiotherapy) method. | In the treatment of idiopathic clubfeet, the Ponseti method and the French functional method have been successful in reducing the need for surgery. The purpose of this prospective study was to compare the results of these two methods at one institution. Patients under three months of age with previously untreated idiopathic clubfeet were enrolled. All feet were rated for severity prior to treatment. After both techniques had been described to them, the parents selected the treatment method. Outcomes at a minimum of two years were classified as good (a plantigrade foot with, or without, a heel-cord tenotomy), fair (a plantigrade foot that had or needed to have limited posterior release or tibialis anterior transfer), or poor (a need for a complete posteromedial surgical release). Two hundred and sixty-seven feet in 176 patients treated with the Ponseti method and 119 feet in eighty patients treated with the French functional method met the inclusion criteria. The patients were followed for an average of 4.3 years. Both groups had similar severity scores before treatment. The initial correction rates were 94.4% for the Ponseti method and 95% for the French functional method. Relapses occurred in 37% of the feet that had initially been successfully treated with the Ponseti method. One-third of the relapsed feet were salvaged with further nonoperative treatment, but the remainder required operative intervention. Relapses occurred in 29% of the feet that had been successfully treated with the French functional method, and all required operative intervention. At the time of the latest follow-up, the outcomes for the feet treated with the Ponseti method were good for 72%, fair for 12%, and poor for 16%. The outcomes for the feet treated with the French functional method were good for 67%, fair for 17%, and poor for 16%. Nonoperative correction of an idiopathic clubfoot deformity can be maintained over time in most patients. Although there was a trend showing improved results with use of the Ponseti method, the difference was not significant. In our experience, parents select the Ponseti method twice as often as they select the French functional method. | 18,978,399 |
Cervical disc arthroplasty compared with arthrodesis for the treatment of myelopathy. | Although there have been case reports describing the use of cervical disc arthroplasty for the treatment of myelopathy, there is a concern that motion preservation may maintain microtrauma to the spinal cord, negatively affecting the clinical results. As we are not aware of any studies on the use of arthroplasty in this scenario, we performed a cross-sectional analysis of two large, prospective, randomized multicenter trials to evaluate the efficacy of cervical disc arthroplasty for the treatment of myelopathy. The patients in the current study were a cohort of patients who were enrolled in the United States Food and Drug Administration Investigational Device Exemption studies of the Prestige ST and Bryan disc replacements (Medtronic, Memphis, Tennessee). The inclusion criteria were myelopathy and spondylosis or disc herniation at a single level from C3 to C7. Clinical outcome measures were collected preoperatively and at six weeks, three months, six months, twelve months, and twenty-four months postoperatively. A total of 199 patients were included in the present study; 106 patients (53%) underwent arthroplasty, whereas ninety-three (47%) underwent arthrodesis. The Neck Disability Index, Short Form-36 scores, and specific arm and neck pain scores improved significantly from baseline at all time points. Patients in all four groups had improvement in the postoperative neurological status and gait function; at twenty-four months after surgery, 90% (95% confidence interval, 77.8% to 96.6%) of the patients in the arthroplasty group and 81% (95% confidence interval, 64.9% to 92.0%) of those in the arthrodesis group had improvement in or maintenance of the neurological status in the Prestige ST trial and 90% (95% confidence interval, 75.8% to 97.1%) of the patients in the arthroplasty group and 77% (95% confidence interval, 57.7% to 90.1%) of those in the arthrodesis group had improvement in or maintenance of the neurological status in the Bryan trial. We found that patients in both the arthroplasty and arthrodesis groups had improvement following surgery; furthermore, improvement was similar between the groups, with no worsening of myelopathy in the arthroplasty group. While the findings at two years postoperatively suggest that arthroplasty is equivalent to arthrodesis for the treatment of cervical myelopathy for a single-level abnormality localized to the disc space, the present study did not evaluate the treatment of retrovertebral compression as occurs in association with ossification of the posterior longitudinal ligament, and we cannot comment upon the treatment of this condition. | 18,978,404 |
Three-dimensional corrective osteotomy of malunited fractures of the upper extremity with use of a computer simulation system. | Three-dimensional anatomical correction is desirable for the treatment of a long-bone deformity of the upper extremity. We developed an original system, including a three-dimensional computer simulation program and a custom-made surgical device designed on the basis of simulation, to achieve accurate results. In this study, we investigated the clinical application of this system using a corrective osteotomy of malunited fractures of the upper extremity. Twenty-two patients with a long-bone deformity of the upper extremity (four with a cubitus varus deformity, ten with a malunited forearm fracture, and eight with a malunited distal radial fracture) participated in this study. Three-dimensional computer models of the affected and contralateral, normal bones were constructed with use of data from computed tomography, and a deformity correction was simulated. A custom-made osteotomy template was designed and manufactured to reproduce the preoperative simulation during the actual surgery. When we performed the surgery, we placed the template on the bone surface, cut the bone through a slit on the template, and corrected the deformity as preoperatively simulated; this was followed by internal fixation. All patients underwent radiographic and clinical evaluations before surgery and at the time of the most recent follow-up. A corrective osteotomy was achieved as simulated in all patients. Osseous union occurred in all patients within six months. Regarding cubitus varus deformity, the humerus-elbow-wrist angle and the anterior tilt of the distal part of the humerus were an average of 2 degrees and 28 degrees, respectively, after surgery. Radiographically, the preoperative angular deformities were nearly nonexistent after surgery. All radiographic parameters for malunited distal radial fractures were normalized. The range of forearm rotation in patients with forearm malunion and the range of wrist flexion-extension in patients with a malunited distal radial fracture improved after surgery. Corrective osteotomy for a malunited fracture of the upper extremity with use of computer simulation and a custom-designed osteotomy template can accurately correct the deformity and improve the clinical outcome. | 18,978,406 |
Effect of micrometer-scale roughness of the surface of Ti6Al4V pedicle screws in vitro and in vivo. | Titanium implants that have been grit-blasted and acid-etched to produce a rough microtopography support more bone integration than do smooth-surfaced implants. In vitro studies have suggested that this is due to a stimulatory effect on osteoblasts. It is not known if grit-blasted and acid-etched Ti6Al4V implants also stimulate osteoblasts and increase bone formation clinically. In this study, we examined the effects of micrometer-scale-structured Ti6Al4V surfaces on cell responses in vitro and on tissue responses in vivo. Ti6Al4V disks were either machined to produce smooth surfaces with an average roughness (Ra) of 0.2 microm or grit-blasted, resulting in an Ra of 2.0, 3.0, or 3.3 microm. Human osteoblast-like cells were cultured on the disks and on tissue culture polystyrene. The cell number, markers of osteoblast differentiation, and levels of local factors in the conditioned media were determined at confluence. In addition, Ti6Al4V pedicle screws with smooth or rough surfaces were implanted into the L4 and L5 vertebrae of fifteen two-year-old sheep. Osteointegration was evaluated at twelve weeks with histomorphometry and on the basis of removal torque. The cell numbers on the Ti6Al4V surfaces were lower than those on the tissue culture polystyrene; the effect was greatest on the roughest surface. The alkaline-phosphatase-specific activity of cell lysates was decreased in a surface-dependent manner, whereas osteocalcin, prostaglandin E(2), transforming growth factor-beta1, and osteoprotegerin levels were higher on the rough surfaces. Bone-implant contact was greater around the rough-surfaced Ti6Al4V screws, and the torque needed to remove the rough screws from the bone was more than twice that required to remove the smooth screws. Increased micrometer-scale surface roughness increases osteoblast differentiation and local factor production in vitro, which may contribute to increased bone formation and osteointegration in vivo. There was a correlation between in vitro and in vivo observations, indicating that the use of screws with rough surfaces will result in better bone-implant contact and implant stability. | 18,978,418 |
Real-time motion-adaptive delivery (MAD) using binary MLC: II. Rotational beam (tomotherapy) delivery. | TomoTherapy delivery is controlled by a planned, projection-wised leaf sequence (sinogram) that is optimized during treatment planning. In this paper, we developed a software solution for real-time motion compensation that delivers helical TomoTherapy plans without modifying the hardware and workflow of the TomoTherapy delivery system. Unlike the dynamic MLC-based method, our technique only requires instantaneous tumor positions, which greatly simplifies its implementation. This technique re-uses the planned sinogram by shuffling its projections and leaf sequences. In order to compensate for longitudinal tumor motion in real-time, instead of sequential execution of the planned sinogram, the projections are executed out of order. That is, we may choose a past or future projection of the planned sinogram rather than the current projection depending on tumor motion, so that the planned radiation source position of the chosen projection is the same as the radiation source position at the current delivery time in the tumor reference frame. The transverse tumor motion is further compensated for by shifting and scaling the leaf open time of the chosen projection. We tested different planned sinograms that were optimized using various synthetic tumor/OAR configurations, as well as planned sinogram of a lung cancer patient, all with zero motion margins. Various TomoTherapy machine parameters and both regular and irregular respiratory traces were used in calculations. By applying the motion-adaptive delivery (MAD) technique, the delivered dose matched the planned dose very well in both DVH and dose profiles. As for the regular and minor irregular respiration, the dose errors were well below 3 mm and 3% criteria. No hot and cold spots were noticeable. For irregular respiration with some missing breathing cycles, this method demonstrates the capability for motion margin reduction. | 18,978,445 |
When to initiate immunotherapy in children with allergic disease? Lessons from the paediatric studies. | Immunotherapy is the only treatment that may alter the natural course of disease. From that perspective, treatment in children might be very valuable. An overview of the recent literature is discussed. The recent literature shows a shift from injectable immunotherapy to noninjectable routes of administration. A systematic review focussing on all forms of immunotherapy in children indicates that there is a lack of high-quality studies to provide evidence for the use of subcutaneous immunotherapy; moreover, evidence for the use of sublingual immunotherapy is still a matter of debate in spite of previous positive meta-analyses. New forthcoming studies may be promising. The 10 years follow-up of the Preventive Allergy Treatment study further underwrites the preventive properties of immunotherapy. Taking the potential preventive action of immunotherapy into account, there is a case to start treatment early in life. However, evidence of the efficacy should be provided by large randomized controlled trials. The lack of high-quality studies with subcutaneous immunotherapy in children requires new studies to fill the gap. The current variation in clinical trials hampers the formulation of clear-cut recommendations on how to perform sublingual immunotherapy (SLIT) in terms of doses, doses schemes, target populations, allergens and specific products from manufacturers. | 18,978,473 |
Sublingual immunotherapy: what have we learnt from the 'big trials'? | Recent systematic reviews support the use of sublingual immunotherapy for allergic rhinoconjunctivitis in adults, whereas data in children have been less convincing. The present review evaluates three recent 'definitive' trials in adults and one in children. Two large independent randomized controlled trials of grass allergen tablets have confirmed the efficacy of sublingual immunotherapy in adults with seasonal allergic rhinoconjunctivitis. Effects were both allergen dose-dependent and time-dependent. Tablets were well tolerated and equally effective in monosensitized compared with polysensitized patients and in patients with peak seasonal asthma (patients with perennial asthma were specifically excluded). Local side effects were common but largely self-limiting and not bothersome. There were no serious treatment-related adverse events. Results were similar in magnitude to those observed in a comparable study of subcutaneous immunotherapy using an alum-based vaccine. A trial of sublingual drops in children with hayfever in a primary care setting was negative, although these results could not be generalized. Sublingual immunotherapy represents an effective and well tolerated treatment for seasonal allergic rhinoconjunctivitis in adults. Current ongoing paediatric trials and evaluation of long-term effects in adults will further define its role in therapy. | 18,978,475 |
The effects of galantamine on psychopathology in chronic stable schizophrenia. | Galantamine is an acetylcholinesterase inhibitor and an allosteric modulator of the alpha4beta2 and alpha7 nicotinic receptors. There are several case reports describing the potential benefits of galantamine for negative symptoms associated with schizophrenia. This secondary analysis describes the effects of galantamine on psychopathology in people with schizophrenia. Subjects with clinically stable chronic schizophrenia were randomized to adjunctive galantamine (24 mg/d) or placebo in a 12-week double-blind trial. Symptomatology was assessed with the Brief Psychiatric Rating Scale (BPRS) and the Clinical Global Impression Scale. The Scale for the Assessment of Negative Symptoms (SANS) was used to measure negative symptoms. Eighty-six patients with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition diagnosis of schizophrenia or schizoaffective disorder taking a stable dose of antipsychotic medications were randomized to adjunctive treatment with study drug (galantamine, n = 42; placebo, n = 44); 73 subjects completed the study (galantamine, n = 35; placebo, n = 38). No significant differences were found on BPRS total score (P = 0.585) or BPRS subfactor scores. Scale for the Assessment of Negative Symptoms total scores also did not decrease significantly (P = 0.106) in either group; however, galantamine treatment was associated with a greater benefit in the SANS subfactor, alogia (P = 0.007). The lack of robust significant effects of galantamine on negative, and other symptom domains, may be due to the relatively low baseline level of these symptoms in the tested population. Galantamine may have some benefit on certain negative symptoms, particularly alogia. Studies specifically designed to address the issue of the efficacy of galantamine for negative symptoms are needed to confirm this observation. | 18,978,489 |
Impulse control disorders arising in 3 patients treated with rotigotine. | We report 3 cases of impulse control disorders (ICDs) that developed in patients with Parkinson disease treated with the novel dopamine agonist, rotigotine. Three patients were identified retrospectively who developed symptoms of an ICD while taking rotigotine. The ICD symptoms developed at 4, 5, and 8 years after diagnosis of Parkinson disease in these patients and while they were taking rotigotine and levodopa. Other drugs included entacapone, amantadine, and selegiline. The first patient developed symptoms of hypersexuality while taking rotigotine 18 mg (40-cm2 patch) daily and levodopa 300 mg/d. The second patient developed pathological gambling while taking rotigotine 22.5 mg (50-cm2 patch) daily and levodopa 300 mg/d. The third patient developed symptoms of hypersexuality, punding, and pathological gambling, losing more than $100,000 while taking rotigotine 18 mg (40-cm2 patch) and levodopa 400 mg/d. In the first 2 patients, the development of the ICD was temporally associated with an increase in rotigotine dosage, whereas the third patient experienced a dramatic increase in his gambling with the addition of rotigotine. Both subjects who developed pathological gambling had a history of recreational gambling for many years, and 1 of the 2 subjects who developed hypersexuality had a history of cross-dressing since childhood. The ICDs in these patients were effectively treated with rotigotine reduction or discontinuation. Rotigotine has the potential for causing ICD, similar to other dopamine agonists. | 18,978,496 |
Long-term use of mood stabilizers and its impact on the quality of life of chinese patients with schizophrenia. | To date, no studies have investigated the prescription patterns of mood stabilizers (MSs) in Chinese patients with schizophrenia. This study examined the frequency and sociodemographic and clinical correlates of MS prescription for outpatients with schizophrenia in Hong Kong (HK) and Beijing (BJ), China. Five hundred five clinically stable outpatients with schizophrenia were randomly selected and interviewed in HK and BJ using standardized assessment instruments. Basic sociodemographic and clinical data and psychotropic drug prescriptions were collected at the time of a diagnostic interview. Thirty-four (6.7%) of the patients were prescribed MSs in the whole sample, with 10.2% and 3.2% of the HK and BJ samples, respectively. Use of MSs was associated with a history of violence, number of admissions, and severity of extrapyramidal side effects. In multiple logistic regression analysis, number of admissions, study site, sex, and length of illness were significantly associated with MSs. Although the ethnic and clinical characteristics of the 2 samples were nearly identical, there was a wide variation in the frequency of MS prescriptions between HK and BJ. | 18,978,504 |
Proteomics blood testing to distinguish chronic rhinosinusitis subtypes. | To evaluate the potential of surface enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) proteomic profiling of serum samples to distinguish chronic rhinosinusitis subtypes. Translational study of serum samples from prospectively enrolled patients undergoing sinus surgery. Patients undergoing endoscopic sinus surgery for chronic rhinosinusitis with nasal polyposis were prospectively enrolled in an ongoing, institutional review board approved proteomics study. SELDI-TOF-MS was performed on 42 serum samples in patients with chronic rhinosinusitis with nasal polyposis (15 patients diagnosed with allergic fungal rhinosinusitis, 10 patients with Samter's triad, and 17 with chronic rhinosinusitis with nasal polyposis). Classification tree analysis on protein spectra developed from peaks detected in the 0 to 100 kD range was performed to identify disease subtypes. SELDI-TOF-MS correctly identified patients with allergic fungal rhinosinusitis from serum samples with 84% sensitivity and 90% specificity, and correctly identified patients with Samter's triad with 88% sensitivity and 88% specificity in two subtype comparison groups. SELDI-TOF-MS correctly identified patients with allergic fungal rhinosinusitis with 76% sensitivity and 82% specificity, and correctly identified patients with Samter's triad with 80% sensitivity and 90% specificity in three subtype comparison groups. The study provides molecular evidence that allergic fungal rhinosinusitis is a discrete subtype of chronic rhinosinusitis. SELDI-TOF-MS is a promising technology that could lead to the development of a rapid blood test, to identify severe chronic rhinosinusitis subtypes. Further investigation into the utility of this technology is warranted. | 18,978,510 |
Nationwide survey of palivizumab for respiratory syncytial virus prevention in Japanese children with congenital heart disease. | A questionnaire study was performed to determine the current status of palivizumab prophylaxis against respiratory syncytial virus infection in Japanese children with congenital heart disease <2 years of age. Palivizumab prophylaxis decreased the respiratory syncytial virus hospitalization rate by 42.8%. | 18,978,515 |
CYP3A7, CYP3A5, CYP3A4, and ABCB1 genetic polymorphisms, cyclosporine concentration, and dose requirement in transplant recipients. | Cyclosporine is a substrate of cytochrome P450 (CYP) 3A and of the transporter ABCB1, for which polymorphisms have been described. In particular, CYP3A5 *3/*3 genotype results in the absence of CYP3A5 activity, whereas CYP3A7 *1/*1C genotype results in high CYP3A7 expression in adults. Log-transformed dose-adjusted cyclosporine trough concentration and daily dose per weight were compared 1, 3, 6, and 12 months after transplantation between CYP3A and ABCB1 genotypes in 73 renal (n = 64) or lung (n = 9) transplant recipients. CYP3A5 expressors (*1/*3 genotype; n = 8-10) presented significantly lower dose-adjusted cyclosporine trough concentrations (P < 0.05) and required significantly higher daily doses per weight (P < 0.01) than the nonexpressors (*3/*3 genotype; n = 55-59) 1, 3, 6, and 12 months after transplantation. In addition, 7 days after transplantation, more CYP3A5 expressors had uncorrected trough cyclosporine concentration below the target concentration of 200 ng/mL than the nonexpressors (odds ratio = 7.2; 95% confidence interval = 1.4-37.3; P = 0.009). CYP3A4 rs4646437C>T influenced cyclosporine kinetics, the T carriers requiring higher cyclosporine dose. CYP3A7*1C carriers required a 1.4-fold to 1.6-fold higher cyclosporine daily dose during the first year after transplantation (P < 0.05). In conclusion, CYP3A4, CYP3A5, and CYP3A7 polymorphisms affect cyclosporine metabolism, and therefore, their genotyping could be useful, in association with therapeutic drug monitoring, to prospectively optimize cyclosporine prescription in transplant recipients. The administration of a CYP3A genotype-dependent cyclosporine starting dose should therefore be tested prospectively in a randomized controlled clinical trial to assess whether it leads to an improvement of the patients outcome after transplantation, with adequate immunosuppression and decreased toxicity. | 18,978,522 |
Pulmonary metastasectomy: a survey of current practice amongst members of the European Society of Thoracic Surgeons. | Currently, no randomized trials exist to guide thoracic surgeons in the field of pulmonary metastasectomy. This study investigates the current clinical practice among European Society of Thoracic Surgeon (ESTS) members. A Web-based questionnaire was created exploring the clinical approach to lung metastasectomy. All ESTS members were surveyed. One hundred forty-six complete responses were received from the 494 consultant ESTS members surveyed (29.6%). For most respondents (68%), lung metastasectomy represents a minor proportion (0-10%) of their clinical volume. Approximately 90% of respondents always/usually review their lung metastasectomy cases within a multidisciplinary meeting. Helical computed tomography is most commonly used (74%) for the detection of metastases, while positron emission tomography is used additionally in less than 50%. Most of respondents (92% and 74%, respectively) consider unresectable primary tumor and predicted incomplete metastasectomy as absolute contraindications to lung metastasectomy. The most frequently performed resection is wedge excision (92%). Palpation of the lung is considered necessary by 65%, while 40% use a thoracoscopic approach with therapeutic intent. Though 65% consider pathologically positive nodes a contraindication to metastasectomy, a similar number rarely/never perform mediastinoscopy before metastasectomy. At the time of metastasectomy 55% perform mediastinal lymph node sampling whereas 33% perform no nodal dissection whatsoever. The survey provides a large, time-sensitive database summarizing the clinical practice of pulmonary metastasectomy by members of the ESTS. Responses demonstrate a remarkable consistency of practice patterns, though certain areas of potential controversy showed greater variance. Conceivably, these divergent approaches will encourage future collaborative studies aimed at identifying evidence-based practices for patients with pulmonary metastases. | 18,978,560 |
Pathway targets to explore in the treatment of non-small cell lung cancer. | With a 5-year survival rate of only 16%, improvements in therapeutic strategies for the treatment of non-small cell lung cancer (NSCLC) are still warranted. Published prognostic gene expression classification signatures in NSCLC overlap poorly across studies. We hypothesized that different NSCLC microarray datasets will share common pathways leading to the identification of new targets for therapeutic development. Per gene mean expression fold change ratios were calculated from 7 publicly-available microarray datasets consisting of a total of 725 profiled samples. This was followed by mapping of differentially expression genes into functionally annotated biologic pathways using Ingenuity pathway analysis software. Common pathways containing genes whose expression levels differed between phenotypic classes defined by NSCLC cases and/or histology, pathologic stage, and gender were determined. Several significant common pathways overlapping these datasets were identified in silico. One of which, Leukocyte Extravasation Signaling pathway, includes targeted agents such as imatinib, dasatinib, and temozolomide currently under exploration in NSCLC trials. The remaining pathways have targets with few drugs developed or under development in cancer therapeutics. Comparison of pathways derived from Eastern versus Western population datasets revealed several differing targets and potential target drugs. This in silico pathway exploration in NSCLC warrants further investigation and could open the door to potential new therapeutics that might improve NSCLC patient outcomes. This strategy can be applied to other cancer types. | 18,978,571 |
Expression of leptin and its functional receptor on disc cells: contribution to cell proliferation. | Human herniated disc tissues and rat nucleus pulposus (NP) cells were used following approval by the authors' institutional Human Ethics Review Committee and Animal Care and Use Committee. To determine the expression of leptin and its functional receptor in herniated disc tissues, and to elucidate whether leptin can stimulate rat NP cells to proliferate in vitro. There is evidence showing that chondrocytes express leptin and functional leptin receptor, and leptin stimulates chondrocyte proliferation in vitro and may play a role in the pathogenesis of osteoarthritis by contributing to osteophyte formation. Intervertebral disc degeneration, similar to osteoarthritis, is also a complicated process in which increased cell proliferation is involved. However, little attention has been paid to the causes of the increased cell proliferation during disc degeneration. Forty-five herniated discs were harvested and immunostained to determine the distribution and type of leptin/functional leptin receptor-expressing cells. The proliferating activity of rat NP cells stimulated with leptin was also evaluated by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and by immunostaining for proliferation cell nuclear antigen (PCNA). Immunohistochemical results from 45 herniated discs showed that leptin/functional leptin receptor-positive cells are commonly seen in cell clusters and proliferating fibrocartilaginous areas, and that the percentage of leptin/functional leptin receptor-positive cells correlates with the age of the patients. Leptin administration led to increased proliferation of rat NP cells in a dose-dependent manner, as shown by MTT assay and by counting the percentage of PCNA-positive cells. Our results suggested that disc cells can express leptin and its functional receptor, that leptin can stimulate proliferation of disc cells in vitro, and therefore that leptin may play a role in the process of intervertebral disc degeneration by contributing to the formation of cell cluster and proliferating fibrocartilaginous tissue. | 18,978,578 |
Neuropathic lower extremity pain following Dunn-McCarthy instrumentation. | Retrospective review of all patients with intact spinal cords, who had posterior spinal fusion (PSF) to the pelvis with Dunn-McCarthy instrumentation. Inclusion criteria were communicative patients with Dunn-McCarthy instrumentation, functioning spinal cords, and sensate lower extremities. We excluded patients with myelomeningocele or spinal cord injury because they are physiologically unable to develop neuropathic lower extremity pain. We distinguished neuropathic lower extremity pain from positional discomfort by eliminating patients whose symptoms resolved in the first postoperative month and patients whose pain persisted greater than a month but did not require treatment or further investigation. To determine the incidence and clinical course of neuropathic lower extremity pain following PSF with Dunn-McCarthy instrumentation. The Dunn-McCarthy technique for instrumented PSF to the pelvis places a rod in close proximity to the L5 nerve root and anterior neurovascular structures. We have treated several patients who developed neuropathic lower extremity pain following PSF with Dunn-McCarthy instrumentation. Seven of 49 patients developed neuropathic pain in a lower extremity after PSF to the pelvis with Dunn-McCarthy instrumentation. Six patients were managed with Neurontin, and 1, with Valium. Two patients were offered removal of their implants, but their symptoms resolved before resection was performed. Pelvic fixation with Dunn-McCarthy instrumentation was associated with a 14% incidence of severe, unilateral neuropathic lower extremity pain. | 18,978,581 |
The effect of pulsed jet lavage in vertebroplasty on injection forces of polymethylmethacrylate bone cement, material distribution, and potential fat embolism: a cadaver study. | In vitro testing of vertebroplasty techniques including pulsed jet-lavage for fat and marrow removal in human cadaveric lumbar and thoracic vertebrae. To develop jet-lavage techniques for vertebroplasty and investigate their effect on cement distribution, injection forces, and fat embolism. The main complications of cement vertebroplasty are cement leakage and pulmonary fat embolism, which can have fatal consequences and are difficult to prevent reliably by current vertebroplasty techniques. Twenty-four vertebrae (Th8-L04) from 5 osteoporotic cadaver spines were grouped in triplets depending on bone mineral density (BMD). Before polymethylmethacrylate (PMMA) vertebroplasty, a pulsatile jet-lavage for removal of intertrabecular fat and bone marrow was performed in 2 groups with 8 specimens each, performing radial and axial irrigation from the biopsy needles. One hundred mL of Ringer solution were injected through 1 pedicle and regained by low vacuum via the contralateral pedicle. Eight control vertebrae were not irrigated. All specimens underwent standardized PMMA cement augmentation injecting 20% of the vertebral volume. Injection forces, cement distribution, and extravasations were quantified. All irrigation solution could be retrieved with the vacuum applied. A Kruskal-Wallis test revealed significantly higher injection forces of the control group as compared with the irrigated groups (P = 0.021). Dilatation of the syringe at forces above 300 N occurred in 75% of the untreated compared with 12.5% of the lavaged specimens. CT distribution analysis showed more homogenous cement distribution of the cement and significantly less extravasation in the irrigated specimens. The developed lavage technique for vertebroplasty showed to be feasible and reproducible. The reduction of injection forces would allow the use of more viscous PMMA cement lowering the risk for cement embolization and results in a safer procedure. The wash-out of bone marrow and the possible reduction of pulmonary fat embolism have to be verified with in vivo models. | 18,978,585 |
Augmentation of pedicle screw fixation strength using an injectable calcium sulfate cement: an in vivo study. | An in vivo landrace model of cement augmentation of pedicle screw was established, and axial pull-out tests and histological analysis were performed. To investigate the long-term in vivo biomechanical performance of pedicle screws augmented with calcium sulfate cement. Little information is available on the long-term biomechanical performance of pedicle screws augmented with calcium sulfate cement in vivo. Ten pedicle screws were implanted into the lumbar vertebrae of 15 adult females landraces weighing 105 to 115 kg. The pedicle screws were augmented with Polymethyl methacrylate (PMMA), augmented with the calcium sulfate cement, or not augmented. The landraces were randomized into 3 study periods of day 1, 6 weeks, and 12 weeks. At the end of the assigned study periods, the animals were killed and axial pull-out tests and histological analyses were conducted on the isolated specimen vertebrae. No significant difference was found among the 1-day, 6-week,and 12-week control group (P > 0.18), no significant difference was found among the 1-day, 6-week and 12-week PMMA group (P > 0.59), and no significant difference was found among the 1-day, 6-week and 12-week calcium sulfate group (P > 0.27). The maximum POS of the PMMA groups was significantly greater than that of the calcium sulfate groups (P < 0.002), the maximum POS of the calcium sulfate groups was significantly greater than that of the control groups (P < 0.004). Histologically progressive absorption of the calcium sulfate was evident. The bone walls around the screws in the 12-week calcium sulfate group were statistically significantly thicker than that of the 12-week control group and that of the 12-week PMMA group. Results of this study demonstrate that the injectable calcium sulfate cement can significantly improve the immediate POS of pedicle screw fixation, and this effect can be maintained even if the calcium sulfate cement has been absorbed completely, which may result from that the calcium sulfate cement resorption paralleled bone ingrowth. | 18,978,590 |
Anterior cervical fusion using a polyetheretherketone cage containing a bovine xenograftp: three to five-year follow-up. | Retrospective review of an anterior polyetheretherketone (PEEK) cage incorporated with a bovine xenograft to treat disorders of the cervical disc. To assess the achievement of fusion by PEEK cage with xenograft radiographically and clinically when used to perform ACDF. Anterior cervical discectomy and fusion is the therapy of choice for degenerative disc disorders of the cervical spine. Although cage device increases initial stability of the levels treated, fusion is the key factor for satisfactory results. Filling the cage devices with autologous iliac bone grafts enable achievement of the best fusion result. Although the volume of harvested bone graft is minimal, donor-site morbidity is still a complication of concern. To avoid this adverse issue, we used a new bovine xenograft in place of autologous bone graft. Fifty-six patients (33 men and 23 women aged 31-78 years) underwent anterior cervical discectomy and fusion using PEEK cage with a bovine xenograft bone substitute to treat symptomatic cervical disorders. Radiographic and clinical results were assessed over 3 to 5 years of follow up. Almost all patients had symptomatic improvement, and 84% reported good-to-excellent satisfaction. All cases achieved solid fusion, confirmed by radiographs and computed tomography, but cage subsidence occurred at 8 levels. As applied in anterior cervical fusion, the cage incorporated with the xenograft prevented donor-site morbidity and provided successful fusion. | 18,978,593 |
Kinematic alterations due to different loading schemes in early acceleration sprint performance from starting blocks. | The purpose of this study was to examine the changes to block start and early acceleration sprint kinematics with resisted sled towing. Ten male sprinters performed 12 sprints (four each of unresisted and approximately 10 and 20% body mass [BM]) for 10 m from a block start. Two-dimensional high-speed video footage (250 Hz) of the starting action and the first three steps of each sprint were recorded to enable the sagittal sprinting kinematic parameters to be obtained using APAS motion analysis software. The overall results of this study indicated that early acceleration sprint performance from starting blocks decreases with increasing load during resisted sled towing. A load of approximately 10% BM had no "negative" effect on sprint start technique or step kinematic variables measured in this study (with the exception of one variable) and was also within the "no greater than 10% decrease in speed" limits suggested by Jakalski. Towing a load of approximately 20% BM increased the time spent in the starting blocks and induced a more horizontal position during the push-off (drive) phase. The approximately 20% BM load also caused the sprinters to shorten their initial strides (length), which may have resulted from the decreased flight distances. Such results suggest that the kinematic changes produced by the 10% BM load may be more beneficial than those of the 20% BM load. Future training studies will, however, need to investigate how these acute changes in sprinting technique impact on long-term adaptations in sprinting performance from resisted sprinting. | 18,978,610 |
Closed-kinetic chain upper-body training improves throwing performance of NCAA Division I softball players. | Closed-kinetic chain resistance training (CKCRT) of the lower body is superior to open-kinetic chain resistance training (OKCRT) to improve performance parameters (e.g., vertical jump), but the effects of upper-body CKCRT on throwing performance remain unknown. This study compared shoulder strength, power, and throwing velocity changes in athletes training the upper body exclusively with either CKCRT (using a system of ropes and slings) or OKCRT. Fourteen female National Collegiate Athletic Association Division I softball player volunteers were blocked and randomly placed into two groups: CKCRT and OKCRT. Blocking ensured the same number of veteran players and rookies in each training group. Training occurred three times weekly for 12 weeks during the team's supervised off-season program. Olympic, lower-body, core training, and upper-body intensity and volume in OKCRT and CKCRT were equalized between groups. Criterion variables pre- and posttraining included throwing velocity, bench press one-repetition maximum (1RM), dynamic single-leg balance, and isokinetic peak torque and power (PWR) (at 180 degrees x s(-1)) for shoulder flexion, extension, internal rotation, and external rotation (ER). The CKCRT group significantly improved throwing velocity by 2.0 mph (3.4%, p < 0.05), and the OKCRT group improved 0.3 mph (0.5%, NS). A significant interaction was observed (p < 0.05). The CKCRT group improved its 1RM bench press to the same degree (1.9 kg) as the OKCRT group (p < 0.05 within each group). The CKCRT group improved all measures of shoulder strength and power, whereas OKCRT conferred little change in shoulder torque and power scores. Although throwing is an open-chain movement, adaptations from CKCRT may confer benefits to subsequent performance. Strength coaches can incorporate upper-body CKCRT without sacrificing gains in maximal strength or performance criteria associated with an athletic open-chain movement such as throwing. | 18,978,626 |
Performance evaluation of a high-speed inertial exercise trainer. | A high-speed, low-resistance inertial exercise trainer (IET, Impulse Training Systems, Newnan, Ga) is increasingly employed in rehabilitative and athletic performance settings. Repetitions on an IET are done through a large range of motion because multijoint movements occur over more than one plane of motion, with no limitation on velocities or accelerations attained. The current study purpose is to assess data reproducibility from an instrumented IET through multiple test-retest measures. Data collection methods required the IET left and right halves to be fitted with a TLL-2K force transducer (Transducer Techniques, Temecula, Calif) on one of its pulleys, and an infrared position sensor (Model CX3-AP-1A, automationdirect.com) located midway on the underside of each track. Signals passed through DI-158U signal conditioners (DATAQ Instruments, Akron, Ohio) and were measured with a four-channel analog data acquisition card at 4000 Hz. To assess data reproducibility, college-age subjects (n = 45) performed four IET workouts that were spaced 1 week apart. Workouts entailed two 60-second sets of repetitive knee- and hip-extensor muscle actions as subjects were instructed to exert maximal voluntary effort. Results from multiple test-retest measures show that the IET elicited reproducible intra- and interworkout data despite the unique challenge of multiplanar and multijoint exercise done over a large range of motion. We conclude that future studies in which IET performance measurement is required may choose to instrument the device with current methodology. Current practical applications include making IET data easier to comprehend for the coaches, athletes, and health care providers who use the device. | 18,978,629 |
Atypical estradiol secretion and ovulation patterns caused by luteal out-of-phase (LOOP) events underlying irregular ovulatory menstrual cycles in the menopausal transition. | The menopausal transition is characterized by irregular menstrual cycles and unpredictable hormone levels, including dramatic swings in estradiol (E2). An increasing number of studies have found variable high E2 and low luteal phase progesterone occur with progression of Stages of Reproductive Aging Workshop (STRAW)stage, but the cause remains unclear. To explore the causes of the erratic changes in E2, individual within-cycle secretion patterns of E2, progesterone, follicle-stimulating hormone, luteinizing hormone, inhibin A, and inhibin B were explored in detail. Blood samples taken three times per week over 1 1/3 menstrual cycles from 77 women aged 21 to 55 classified as mid-reproductive age (STRAW stages 5 and 4; n = 21), late-reproductive age (STRAW stages 4 and 3; n = 16), early menopausal transition (STRAW stage 2; n = 17), and late menopausal transition (STRAW stage 1; n = 23) were analyzed. Eleven of the 29 (37%) early and late menstrual transition ovulatory cycles exhibited a specific pattern of E2 secretion that was characterized by a second increase in E2 during the mid- and late luteal phases and that continued to a peak during the subsequent menstrual phase. This second rise and fall in E2 was typical in appearance of a normal follicular phase, except that it was superimposed on an existing ovulatory cycle(specifically during the luteal and menstrual phases). The pattern was therefore referred to as a luteal out-of-phase(LOOP) follicular event. In four of these LOOP cycles, a luteinizing hormone peak and ovulatory episode followed the second E2 peak early in the subsequent cycle. Compared with the typical ovulatory cycles, the cycles with LOOP events exhibited lower luteal phase progesterone, higher early cycle follicle-stimulating hormone, and lower early cycle inhibin B. They were also associated with abnormally short (<21 d) or long (>40 d) cycle length. Many of the marked increases in ovulatory cycle E2 and cycle irregularities during the menopausal transition may be due to LOOP events and appear to be triggered by prolonged high follicular phase follicle-stimulating hormone levels. | 18,978,637 |
A familial CHARGE syndrome with a CHD7 nonsense mutation and new clinical features. | The autosomal dominant CHARGE syndrome (MIM musical sharp214800) is caused by mutations in the CHD7 gene. It is usually sporadic but a few cases with gonadal mosaicism and familial inheritance have been reported. We describe a familial CHARGE syndrome in a two-generation Finnish family with a nonsense mutation in the CHD7 gene. Detailed clinical examination of the affected family members was performed, and mutations in the CHD7 gene were analysed with direct sequencing and multiplex ligation-dependent probe amplification. A nonsense mutation, p.Q1599X, was detected in exon 21 of the CHD7 gene in three affected family members. The father was only mildly affected, whereas his son had a very severe manifestation of the syndrome, causing death at the age of 3 months. The second pregnancy was prematurely terminated in the 23rd week because of cardiac anomalies detected in the ultrasound scan. The father's brother also had mild symptoms, but no mutation was detected in him. In this report, the variability of clinical symptoms within families and the clinical importance of mildly affected patients with the CHARGE syndrome are underlined with implications for molecular genetic diagnostics of the syndrome. Features not described in the CHARGE syndrome before are also presented. | 18,978,652 |
Tests and measures used by specialist physical therapists when examining patients with stroke. | Examination procedures preferred by physical therapists have not been documented either specifically or comprehensively. The purpose of this study was to determine which tests and measures are used most frequently by specialists in the examination of adults with stroke. Physical therapy specialists were identified as having geriatric or neurologic certification through the American Board of Physical Therapy Specialties. A request to participate in a Web-based survey was sent to 471 individuals in the American Physical Therapy Association's Directory of Certified Specialists. A comprehensive list of tests and measures was first derived from the Interactive Guide to Physical Therapist Practice. The list was finalized based on several exclusion criteria and the results of a pilot study. Subjects rated the frequency of use of 294 tests and measures with patients post-stroke on a Likert scale. The survey response rate was 31.7% (n = 128). The 50 most frequently used tests and measures were identified. The results of this study do not identify the tests and measures that clinicians should use, only those that the specialists use. Nevertheless, clinicians may want to consider tests and measurements frequently used by specialists when examining adults with stroke. | 18,978,668 |
Influence of spray-dried hydroxyapatite-5-fluorouracil granules on cell lines derived from tissues of mesenchymal origin. | In our previous work we described the preparation and characterization of spray dried hydroxyapatite micro granules loaded with 5-fluorouracil (5-FU). These loaded particles are used as a model drug delivery system (DDS). In this study we examined the in vitro response of two cell lines derived from different tissues to 5-FU loaded granules (LG). Both cell lines, either L929 cells of a mouse fibroblast lineage or cells originating from a rat osteosarcoma (ROS 17/2.8) showed a dose dependent decrease in cell proliferation in response to 5-FU-, either dissolved in the culture medium or loaded onto particles. The response of the two cell lines to loaded and nonloaded particles was different. The effect of LG and of a corresponding concentration of free 5-FU was practically the same for the ROS 17/2.8 cells indicating that ROS 17/2.8 cells were not affected by the carrier material. In contrast, L929 cells showed a slight decrease in cell proliferation also in the presence of granules not loaded with 5-FU. This is thought to be attributed to the inhibition of mitogenesis by phosphocitrates, already demonstrated in fibroblasts. In summary, we found that the loaded 5-FU kept its effectivity after the spray drying process and that the response towards the granules varied with cell type. This is the first step towards a tissue specific DDS. | 18,978,702 |
Progressive rise of c fos expression from premalignant to malignant lesions of oral cavity. | Oral cancer is a worldwide phenomenon. It is thought to develop in a number of premalignant lesions. Protooncogene c fos is a known transformer of premalignant to malignant lesions. However, its role in oral carcinogenesis is not yet known. A total of 130 cases were studied comprising of premalignant lesions (n=50), squamous cell carcinoma (n=50) and controls (n=30). c fos expression was studied by immunohistochemistry. Premalignant lesions of oral cavity occurred at a lower age group (mean 39.2 years) compared to squamous cell carcinoma (mean 51.8 years), p <0.001. Mean c fos percentage positivity in squamous cell carcinomas (SCC), premalignant lesions and controls was 44.5+/-36.9%, 11.4+/-18.8% and 1.23+/-2.6% respectively, the differences were highly significant (p<0.001). c fos positivity also increased from mild (10.85+/-14.23%) to moderate dysplasia (19.64 +/-26.05%). The serially increasing c fos expression from normal mucosa to premalignant lesions to SCC and in dysplasias suggests that it could be an early gene to get activated and form transcription factor activator protein -1(AP-1). | 18,978,706 |
Cell proliferation and apoptosis in keratocystic odontogenic tumors. | Keratocystic odontogenic tumors (KOTs), also known as odontogenic keratocysts, were recently classified as a benign neoplasia due to the aggressive clinical behavior. Although several studies have shown the high proliferative activity of the epithelial lining, few studies have evaluated apoptosis in KOTs. Therefore, the aim of this study is to evaluate and compare the proliferation index (PI) and the apoptotic index (AI) of the epithelial lining in sporadic KOTs, KOTs associated with the Nevoid Basal Cell Carcinoma Syndrome (NBCCS KOTs), and dentigerous cysts. A total of 11 sporadic KOTs, 15 NBCCS KOTs, and 11 dentigerous cysts were evaluated. The PI was assessed by immunohistochemical detection of the cell proliferation marker Ki-67. The AI was assessed by morphological evaluation of sections stained by methyl green-pyronin. The TUNEL assay was used to confirm the occurrence of apoptosis. Differences in the PI and the AI between sporadic KOTs, NBCCS KOTs, and dentigerous cysts were analyzed using the Kruskal-Wallis test. Differences in the PI and the AI between the epithelial layers of each lesion were analyzed using the Wilcoxon test. The PI and AI were higher in sporadic and NBCCS KOTs than in dentigerous cysts. No difference in these indexes was observed between sporadic and NBCCS KOTs. In dentigerous cysts, the PI was higher in the basal layer. In sporadic and NBCCS KOTs, the PI was higher in suprabasal layer. No difference in the AI was observed between the basal layer and the suprabasal layer in the three lesions. The AI was higher in the superficial layer of sporadic and NBCCS KOTs. The present study demonstrates that the epithelial lining of KOTs shows a distinct pattern of cell proliferation and apoptosis, reflecting its high cell turnover and reinforcing its classification as an odontogenic tumor. | 18,978,709 |
Prevalence of oral lesions in patients with psoriasis. | To determine the prevalence of oral lesions (OL) in patients with psoriasis, and compare these findings with the ones found in patients without this condition. In the present observational and comparative study, we evaluated 207 patients, with and without psoriasis, attending the dermatological consulting service of a concentration hospital in Mexico City. The possible association between OL and psoriasis was analyzed through a logistic regression model; the Odds Ratio (OR) and its Confidence Interval (CI) was calculated to be 95%. Two hundred and seven cases were examined (80 with psoriasis and 127 without psoriasis). Of these, 75 (36.2%) were men and 132 (63.7%) women. Oral lesions were found in 54 (67.5%) psoriatic patients and in 63 (49.6%) of the comparative group (p <0.012). Fissured tongue (FT) was present in 47.5 % of the patients with psoriasis and in 20.4 % of the group without psoriasis, (OR=3.46, 95% CI [1.14, 10.5], p=0.001). Geographic tongue (GT) was present in 12.5 % of the group with psoriasis and 4.7 % in the group without this disease (OR=3.54 95 % CI [1.97, 6.79], p=0.028). Likewise, six patients (7.5 %) with psoriasis and 3 (2.36 %) from the comparative group presented simultaneously GT and FT (p = 0.0776). The most frequent type of psoriasis was the vulgar psoriasis (90 %), in which a higher prevalence of FT (p <0.05) was present. There were no differences between both groups (p>0.05) regarding the use of tobacco. Alcohol consumption was greater (55.0%) among patients with psoriasis than among those without psoriasis (26.7%) (p<0.05), but when the association with GT and FT was analyzed, no significant differences were found among consumers and not consumers of tobacco and alcohol (p> 0.05). The high prevalence of GT and FT in patients with psoriasis suggests that these lesions should be taken into account in new studies as possible predictors or markers of the severity of this dermatosis, in order to confirm the association of these entities. | 18,978,710 |
Inferior alveolar nerve transposition with involvement of the mental foramen for implant placement. | Inferior Alveolar Nerve (IAN) transposition is an option for prosthetic rehabilitation in cases of moderate or even severe bone reabsorption for patients that do not tolerate removable dentures. The aim of the present report is to describe an inferior alveolar nerve transposition with involvement of the mental foramen for implant placement. The surgical procedure was performed under local anesthesia, by the inferior alveolar, lingual and buccal nerve blocking technique. Centripetal osteotomy was performed, and bone tissue was removed, leaving the nerve tissue free in the foramen area. After that, transsection of the incisor nerve was performed, and lateral osteotomy was started from the buccal direction, toward the trajectory of the IAN. The procedure was concluded, by making use of a delicate resin spatula to manipulate the vascular-nervous bundle. The drilling sequence for placing the dental implants was performed, and autogenous bone was harvested using a bone collector attached to the surgical suction appliance. After the implants were placed, the bone tissue previously collected during the osteotomies and drilling processes was placed in order to protect the IAN from contact with the implants. The surgical protocol for inferior alveolar nerve transposition, followed by implant placement presented excellent results, with complete recovery of the sensitivity, seven months after the surgical procedure. | 18,978,714 |
Y-Box-binding protein-1 is a promising predictive marker of radioresistance and chemoradioresistance in nasopharyngeal cancer. | The Y-Box-binding protein-1, a member of the cold-shock domain DNA- and RNA-binding protein superfamily, is known to mediate chemoresistance. The aim of this study was to determine the expression of Y-Box-binding protein-1 in nasopharyngeal cancer in vitro and in tumor tissue samples as well as analyze the clinicopathological significance of Y-Box-binding protein-1 expression in nasopharyngeal cancer, in particular as a predictor of outcome after treatment. The Y-Box-binding protein-1 expression profile was evaluated at the mRNA and protein levels in poorly differentiated CNE-2 nasopharyngeal cancer cells by real-time RT-PCR, western blot analysis and immunohistochemistry. Y-Box-binding protein-1 expression in 143 nasopharyngeal cancer specimens was examined by immunohistochemistry and correlated with clinicopathologic parameters. Y-Box-binding protein-1 mRNA and protein were found to be expressed in CNE-2 nasopharyngeal cancer cells in vitro. Of 143 patient tissue sections, 137 (96%) were stained positive for the Y-Box-binding protein-1 protein. Y-Box-binding protein-1 immunostaining was observed to be predominantly cytoplasmic. A higher recurrence of nasopharyngeal cancer was found in patients whose tissues had increased Y-Box-binding protein-1 expression (P<0.001). The Cox proportionate hazard regression model also established that high Y-Box-binding protein-1 immunoreactivity was significantly correlated with increased risk (2.13 times) of recurrence as compared to low Y-Box-binding protein-1 immunoreactivity (P=0.01). Within groups of patients treated by radiotherapy or chemoradiotherapy, recurrent cases had significantly higher Y-Box-binding protein-1 expression than nonrecurrent cases (P<0.001 and P=0.0035, respectively). These data suggest that Y-Box-binding protein-1 expression has clinicopathological significance with potential as a predictive marker of recurrence in nasopharyngeal cancer patients who undergo radiotherapy or chemoradiotherapy. | 18,978,732 |
Metachromatic leukodystrophy: an overview of current and prospective treatments. | Nowadays, different treatment options are available for an extending list of lysosomal storage diseases (LSDs). Hematopoietic stem cell transplantation (HSCT) can benefit selected subsets of patients with some LSDs, but results have been poor in several other disorders, including metachromatic leukodystrophy (MLD), outlining the need for innovative therapeutic approaches in this field. Enzyme replacement therapy has been developed recently for MLD, and a Phase I/II trial is ongoing. However, the blood-brain barrier limits the access of the recombinant product to the nervous tissues. Autologous hematopoietic stem/progenitor cells can be genetically modified to constitutively express supra-physiological levels of arylsulfatase-A and may become a quantitatively more effective source of functional enzyme than normal donor cells when transplanted in patients with MLD, thus possibly overcoming the limits of HSCT. Moreover, autologous transplantation might be associated with a significantly reduced transplant-related morbidity and TRM avoiding the risk of GVHD. Therefore, such a gene therapy strategy could represent a significant advance in comparison to conventional allogeneic HSCT. | 18,978,739 |
Teasing, disordered eating behaviors, and psychological morbidities among overweight adolescents. | To assess whether weight-related teasing is associated with weight control behaviors, disordered eating thoughts and behaviors, and psychological comorbidities in overweight adolescents. A sample of 46 male and 84 female adolescents completed a survey assessing teasing frequency, sources of teasing (peers and family), weight control behaviors, disordered eating thoughts and behaviors, depression, anxiety, anger, and self-esteem. Frequent teasing by both family and peers was associated with greater disordered eating thoughts and behaviors, depression, anxiety, anger, and decreased self-esteem. The more that adolescents were bothered by peer and family teasing, the more often they reported a greater value on thinness, higher levels of anxiety, lower self-esteem, and their self-assessment was influenced by their weight and shape. Higher levels of teasing frequency and being bothered by teasing were related to greater odds of adolescents endorsing severe levels of binge eating behaviors and depressive symptomolgy. Overweight adolescents teased about their weight are at risk for disordered eating thoughts and behaviors and psychological morbidities. Health-care providers should involve parents and youth in discussing teasing concerns. Furthermore, parents, schools, and communities should consider enacting policies to decrease or prohibit teasing. Future research is needed to further explore relationships between teasing and psychological functioning. | 18,978,759 |
Expression of 24,426 human alternative splicing events and predicted cis regulation in 48 tissues and cell lines. | Alternative pre-messenger RNA splicing influences development, physiology and disease, but its regulation in humans is not well understood, partially because of the limited scale at which the expression of specific splicing events has been measured. We generated the first genome-scale expression compendium of human alternative splicing events using custom whole-transcript microarrays monitoring expression of 24,426 alternative splicing events in 48 diverse human samples. Over 11,700 genes and 9,500 splicing events were differentially expressed, providing a rich resource for studying splicing regulation. An unbiased, systematic screen of 21,760 4-mer to 7-mer words for cis-regulatory motifs identified 143 RNA 'words' enriched near regulated cassette exons, including six clusters of motifs represented by UCUCU, UGCAUG, UGCU, UGUGU, UUUU and AGGG, which map to trans-acting regulators PTB, Fox, Muscleblind, CELF/CUG-BP, TIA-1 and hnRNP F/H, respectively. Each cluster showed a distinct pattern of genomic location and tissue specificity. For example, UCUCU occurs 110 to 35 nucleotides preceding cassette exons upregulated in brain and striated muscle but depleted in other tissues. UCUCU and UGCAUG seem to have similar function but independent action, occurring 5' and 3', respectively, of 33% of the cassette exons upregulated in skeletal muscle but co-occurring for only 2%. | 18,978,788 |
Deep surveying of alternative splicing complexity in the human transcriptome by high-throughput sequencing. | We carried out the first analysis of alternative splicing complexity in human tissues using mRNA-Seq data. New splice junctions were detected in approximately 20% of multiexon genes, many of which are tissue specific. By combining mRNA-Seq and EST-cDNA sequence data, we estimate that transcripts from approximately 95% of multiexon genes undergo alternative splicing and that there are approximately 100,000 intermediate- to high-abundance alternative splicing events in major human tissues. From a comparison with quantitative alternative splicing microarray profiling data, we also show that mRNA-Seq data provide reliable measurements for exon inclusion levels. | 18,978,789 |
Lung cancer susceptibility locus at 5p15.33. | We carried out a genome-wide association study of lung cancer (3,259 cases and 4,159 controls), followed by replication in 2,899 cases and 5,573 controls. Two uncorrelated disease markers at 5p15.33, rs402710 and rs2736100 were detected by the genome-wide data (P = 2 x 10(-7) and P = 4 x 10(-6)) and replicated by the independent study series (P = 7 x 10(-5) and P = 0.016). The susceptibility region contains two genes, TERT and CLPTM1L, suggesting that one or both may have a role in lung cancer etiology. | 18,978,790 |
Increased nucleotide polymorphic changes in the 5'-untranslated region of delta-catenin (CTNND2) gene in prostate cancer. | Cancer pathogenesis involves multiple genetic and epigenetic alterations, which result in oncogenic changes in gene expression. delta-Catenin (CTNND2) is overexpressed in cancer, although the mechanisms of its upregulation are highly variable. Here we report that in prostate cancer, the methylation of CpG islands in the delta-catenin promoter was not a primary regulatory event. There was also no delta-catenin gene amplification. However, using the single-strand conformation polymorphism analysis, we observed the increased nucleotide changes in the 5'-untranslated region of delta-catenin gene in human prostate cancer. At least one such change (-9 G>A) is a true somatic point mutation associated with a high Gleason's score, poorly differentiated prostatic adenocarcinoma. Laser capture microdissection coupled with PCR analyses detected the mutation only in cancerous but not in the adjacent benign prostatic tissues. Using chimeric genes encoding the luciferase reporter, we found that this mutation, but not a random mutation or a mutation that disrupts an upstream open reading frame, resulted in a remarkably higher expression and enzyme activity. This mutation did not affect transcriptional efficiency, suggesting that it promotes delta-catenin translation. This is the first report of delta-catenin gene mutation in cancer and supports the notion that multiple mechanisms contribute to its increased expression in carcinogenesis. | 18,978,817 |
Adaptation and perceptual norms in color vision. | Many perceptual dimensions are thought to be represented relative to an average value or norm. Models of norm-based coding assume that the norm appears psychologically neutral because it reflects a neutral response in the underlying neural code. We tested this assumption in human color vision by asking how judgments of "white" are affected as neural responses are altered by adaptation. The adapting color was varied to determine the stimulus level that did not bias the observer's subjective white point. This level represents a response norm at the stages at which sensitivity is regulated by the adaptation, and we show that these response norms correspond to the perceptually neutral stimulus and that they can account for how the perception of white varies both across different observers and within the same observer at different locations in the visual field. We also show that individual differences in perceived white are reduced when observers are exposed to a common white adapting stimulus, suggesting that the perceptual differences are due in part to differences in how neural responses are normalized. These results suggest a close link between the norms for appearance and coding in color vision and illustrate a general paradigm for exploring this link in other perceptual domains. | 18,978,861 |
Plurality of principal angles for a given pseudo-Brewster angle when polarized light is reflected at a dielectric-conductor interface. | The pseudo-Brewster angle phi(pB) of minimum reflectance for p-polarized light and the principal angle phi at which incident linearly polarized light of the proper azimuth is reflected circularly polarized are considered as functions of the complex relative dielectric function epsilon of a dielectric-conductor interface over the entire complex epsilon plane. In particular, the spread of phi for a given phi (pB) is determined, and the maximum difference(phi -phi(pB))(max) is obtained as a function of phi(pB). The maximum difference (phi -phi(pB))(max) approaches 45 degrees and 0 in the limit as phi(pB)-->phi 0 and 90 degrees , respectively. For phi(pB)<22.666 degrees , multiple principal angles phi (i), i=1,2,3, appear for each epsilon in a subdomain of fractional optical constants. This leads to an elaborate pattern of multiple solution branches for the difference phi (i)-phi(pB), i=1,2,3, as is illustrated by several examples. | 18,978,867 |
Temperature dependence of a macrobending edge filter based on a high-bend loss fiber. | The temperature dependence of a macrobending bare-fiber-based edge filter is investigated both theoretically and experimentally. The fiber used is a high-bend loss fiber, type 1060XP. The experimental results show a good agreement with the proposed theoretical model over a temperature range from 0 degrees C to 80 degrees C. It is shown that the strong temperature dependence of a high-bend loss fiber has a significant influence on the performance of a fiber edge filter used in a wavelength measurement application. However, it is also concluded that such a temperature-dependent performance can be beneficially utilized in a fiber temperature sensing application. | 18,978,890 |
Experimental investigation of combined four-wave mixing and Raman effect in the normal dispersion regime of a photonic crystal fiber. | We study the effect of stimulated Raman scattering on four-wave mixing sidebands generated by pumping in the normal dispersion regime of a photonic crystal fiber. Q-switch nanosecond pulses at 1064 nm are used to generate signal and idler wavelengths by degenerate four-wave mixing. These three waves generate their own Raman Stokes orders, leading to a broadband supercontinuum. | 18,978,896 |
Fluorescence monitoring of microchip capillary electrophoresis separation with monolithically integrated waveguides. | Using femtosecond laser writing, optical waveguides were monolithically integrated into a commercial microfluidic lab-on-a-chip device, with the waveguides intersecting a microfluidic channel. Continuous-wave laser excitation through these optical waveguides confines the excitation window to a width of 12 microm, enabling high-resolution monitoring of the passage of different types of fluorescent analytes when migrating and being separated in the microfluidic channel by microchip capillary electrophoresis. Furthermore, we demonstrate on-chip-integrated waveguide excitation and detection of a biologically relevant species, fluorescently labeled DNA molecules, during microchip capillary electrophoresis. Well-controlled plug formation as required for on-chip integrated capillary electrophoresis separation of DNA molecules, and the combination of waveguide excitation and a low limit of detection, will enable monitoring of extremely small quantities with high spatial resolution. | 18,978,901 |
Cancellation of Raman pulse walk-off by slow light. | We theoretically demonstrate in a nonlinear optical fiber system with a narrowband Raman gain that pulse walk-off between the pump and the Raman Stokes waves can be fully compensated for by Raman slow light, leading to group-velocity matching between the interacting waves, greater useful interaction length, and thereby enhanced Raman amplification efficiency. Limitations due to Kerr effect are further discussed. | 18,978,902 |
Dual-channel optical phase measurement system for improved precision. | Developments and applications of a dual-channel phase measurement system are being proposed and experimentally studied by utilizing an optical homodyne technique. In this measurement system, the phase modulation was adopted by using a near-stable Zn-indiffused lithium niobate phase modulator. The proposed method was successfully applied on the simultaneous measurements of the phase-retardation difference between a transmitted light and a reflected light after passing through a nonpolarization beam splitter. The measured stability of the phase-retardation difference was approximately 0.0013 rad. | 18,978,910 |
Improved design of polarization-maintaining photonic crystal fibers. | We propose the realization of single-polarization operation in highly birefringent photonic crystal fibers. The suppression of one of the polarization states is realized by introducing index-matched cladding defect waveguides. The leakage loss of the index-matched polarization state can be enhanced by nearly 4 orders of magnitude. In particular, polarization-dependent loss larger than 2.97 dB/m with transmission loss lower than 0.03 dB/m in a wavelength region ranging from 1.54 to 1.566 microm can be realized in one such fiber. | 18,978,914 |
Two-color surface lattice solitons. | We study the properties of surface solitons generated at the edge of a semi-infinite photonic lattice in nonlinear quadratic media, namely two-color surface lattice solitons. We analyze the impact of phase mismatch on the existence and stability of nonlinear surface modes and find novel classes of two-color twisted surface solitons, which are stable in a large domain of their existence. | 18,978,917 |
Adolescents' performance on delay and probability discounting tasks: contributions of age, intelligence, executive functioning, and self-reported externalizing behavior. | Healthy adolescents, ages 9-23, completed delay and probability discounting tasks and measures of verbal and nonverbal intelligence, executive functioning, and self-reported internalizing and externalizing behavior. Delay but not probability discounting decreased with age. Delay discounting was also associated with verbal intelligence and Go-NoGo and Iowa Gambling Task performance. Probability discounting was associated only with externalizing behavior. Findings conform to an accumulation of evidence that while delay and probability discounting may have some overlapping components, they also reflect some fundamentally different processes in this age group. | 18,978,926 |
Neural network approaches and their reproducibility in the study of verbal working memory and Alzheimer's disease. | As clinical and cognitive neurosciences mature, the need for sophisticated neuroimaging analysis becomes more apparent. Multivariate analysis techniques have recently received increasing attention because they have attractive features that cannot be easily realized by the more commonly used univariate, voxel-wise, techniques. Multivariate approaches evaluate correlation/covariance of activation across brain regions, rather than proceeding on a voxel-by-voxel basis. Thus, their results can be more easily interpreted as a signature of neural networks. Univariate approaches, in contrast, cannot directly address functional connectivity in the brain. Apart from this conceptual difference, the covariance approach can also result in greater statistical power when compared with univariate techniques, which are forced to employ very stringent, and often overly conservative, corrections for voxel-wise multiple comparisons. Multivariate techniques also lend themselves much better to prospective application of results from the analysis of one dataset to entirely new datasets. We provide two examples that illustrate different uses of multivariate techniques in cognitive and clinical neuroscience. We hope this contribution helps facilitate wider dissemination of these techniques in the research community. | 18,978,933 |
Of Asian forests and European fields: Eastern U.S. plant invasions in a global floristic context. | Biogeographic patterns of species invasions hold important clues to solving the recalcitrant 'who', 'where', and 'why' questions of invasion biology, but the few existing studies make no attempt to distinguish alien floras (all non-native occurrences) from invasive floras (rapidly spreading species of significant management concern), nor have invasion biologists asked whether particular habitats are consistently invaded by species from particular regions. Here I describe the native floristic provenances of the 2629 alien plant taxa of the Eastern Deciduous Forest of the Eastern U.S. (EUS), and contrast these to the subset of 449 taxa that EUS management agencies have labeled 'invasive'. Although EUS alien plants come from all global floristic regions, nearly half (45%) have native ranges that include central and northern Europe or the Mediterranean (39%). In contrast, EUS invasive species are most likely to come from East Asia (29%), a pattern that is magnified when the invasive pool is restricted to species that are native to a single floristic region (25% from East Asia, compared to only 11% from northern/central Europe and 2% from the Mediterranean). Moreover, East Asian invaders are mostly woody (56%, compared to just 23% of the total alien flora) and are significantly more likely to invade intact forests and riparian areas than European species, which dominate managed or disturbed ecosystems. These patterns suggest that the often-invoked 'imperialist dogma' view of global invasions equating invasion events with the spread of European colonialism is at best a restricted framework for invasion in disturbed ecosystems. This view must be superseded by a biogeographic invasion theory that is explicitly habitat-specific and can explain why particular world biotas tend to dominate particular environments. | 18,978,940 |
Osteoclasts are active in bone forming metastases of prostate cancer patients. | Bone forming metastases are a common and disabling consequence of prostate cancer (CaP). The potential role of osteoclast activity in CaP bone metastases is not completely explained. In this study, we investigated ex vivo whether the osteolytic activity is present and how it is ruled in CaP patients with bone forming metastases. Forty-six patients affected by newly diagnosed CaP and healthy controls were enrolled. At diagnosis, 37 patients had a primary tumour only, while 9 had primary tumour and concomitant bone forming metastases. In all patients there was no evidence of metastasis to other non-bone sites. For all patients and controls we collected blood and urinary samples. We evaluated patients' bone homeostasis; we made peripheral blood mononuclear cell (PBMC) cultures to detect in vitro osteoclastogenesis; we dosed serum expression of molecules involved in cancer induced osteoclatogenesis, such as RANKL, OPG, TNF-alpha, DKK-1 and IL-7. By Real-Time PCR, we quantified DKK-1 and IL-7 gene expression on micro-dissected tumour and healthy tissue sections. CaP bone metastatic patients showed bone metabolism disruption with increased bone resorption and formation compared to non-bone metastatic patients and healthy controls. The CaP PBMC cultures showed an enhanced osteoclastogenesis in bone metastatic patients, due to an increase of RANKL/OPG ratio. We detected increased DKK-1 serum levels and tissue gene expression in patients compared to controls. IL-7 resulted high in patients' sera, but its tissue gene expression was comparable in patients and controls. We demonstrated ex vivo that osteoclastogenesis is an active mechanism in tumour nesting of bone forming metastatic cancer and that serum DKK-1 levels are increased in CaP patients, suggesting to deeply investigate its role as tumour marker. | 18,978,943 |
Squamous cell carcinoma of the external auditory canal. | This study aims to analyze the treatments, prognostic variables, and outcomes of patients with squamous cell carcinomas (SCC) of the external auditory canal (EAC) and middle ear treated in our department over a 15-year period. A retrospective analysis of 19 patients treated in our department between 1990 and 2006. The patients were staged according to the Pittsburgh classification. Patients were treated with either a lateral (LTBR) or an extended temporal bone resection (total or subtotal). Parotidectomy was performed in patients with suspected clinical or radiological invasion and postoperative radiotherapy was the adjuvant treatment in most patients in advanced stages. The overall 5-year survival was 37%. There were no patients in stage I. The survival rates were 100%, 25%, and 16% for stages II, III, and IV, respectively. Facial nerve paralysis (p = 0.007) and lymph node involvement (p = 0.006) were associated with decreased survival rates. SCC of the temporal bone are rare but have a poor prognosis. Lymph node involvement and facial nerve palsy are associated with a poorer outcome. These tumors must initially be treated radically, for which an early diagnosis is important. | 18,978,963 |
Intracranial enterogenous cyst extending into both supratentorial and infratentorial compartments: case report and review of the literature. | Intracranial enterogenous cysts are rare. There have been only two cases reported of such cysts that extended into both the infratentorial and supratentorial compartments. We add a third case and review the literature to assess their pathogenesis, clinical features, and management. | 18,978,968 |
Chemotactic response of marine micro-organisms to micro-scale nutrient layers. | The degree to which planktonic microbes can exploit microscale resource patches will have considerable implications for oceanic trophodynamics and biogeochemical flux. However, to take advantage of nutrient patches in the ocean, swimming microbes must overcome the influences of physical forces including molecular diffusion and turbulent shear, which will limit the availability of patches and the ability of bacteria to locate them. Until recently, methodological limitations have precluded direct examinations of microbial behaviour within patchy habitats and realistic small-scale flow conditions. Hence, much of our current knowledge regarding microbial behaviour in the ocean has been procured from theoretical predictions. To obtain new information on microbial foraging behaviour in the ocean we have applied soft lithographic fabrication techniques to develop 2 microfluidic devices, which we have used to create (i) microscale nutrient patches with dimensions and diffusive characteristics relevant to oceanic processes and (ii) microscale vortices, with shear rates corresponding to those expected in the ocean. These microfluidic devices have permitted a first direct examination of microbial swimming and chemotactic behaviour within a heterogeneous and dynamic seascape. The combined use of epifluorescence and phase contrast microscopy allow direct examinations of the physical dimensions and diffusive characteristics of nutrient patches, while observing the population-level aggregative response, in addition to the swimming behaviour of individual microbes. These experiments have revealed that some species of phytoplankton, heterotrophic bacteria and phagotrophic protists are adept at locating and exploiting diffusing microscale resource patches within very short time frames. We have also shown that up to moderate shear rates, marine bacteria are able to fight the flow and swim through their environment at their own accord. However, beyond a threshold high shear level, bacteria are aligned in the shear flow and are less capable of swimming without disturbance from the flow. Microfluidics represents a novel and inexpensive approach for studying aquatic microbial ecology, and due to its suitability for accurately creating realistic flow fields and substrate gradients at the microscale, is ideally applicable to examinations of microbial behaviour at the smallest scales of interaction. We therefore suggest that microfluidics represents a valuable tool for obtaining a better understanding of the ecology of microorganisms in the ocean. | 18,979,007 |
Injection of dsRNA into female A. aegypti mosquitos. | Reverse genetic approaches have proven extremely useful for determining which genes underly resistance to vector pathogens in mosquitoes. This video protocol illustrates a method used by the James lab to inject dsRNA into female A. aegypti mosquitoes, which harbor the dengue virus. The technique for calibrating injection needles, manipulating the injection setup, and injecting dsRNA into the thorax is illustrated. | 18,979,015 |
Protocol for mosquito rearing (A. gambiae). | This protocol describes mosquito rearing in the insectary. The insectary rooms are maintained at 28 degrees C and approximately 80% humidity, with a 12 hr. day/night cycle. For this procedure, you'll need mosquito cages, 10% sterile sucrose solution, paper towels, beaker, whatman filter paper, glass feeders, human blood and serum, water bath, parafilm, distilled water, clean plastic trays, mosquito food (described below), mosquito net to cover the trays, vacuum, and a collection chamber to collect adults. | 18,979,019 |
Predicting the effectiveness of population replacement strategy using mathematical modeling. | Charles Taylor and John Marshall explain the utility of mathematical modeling for evaluating the effectiveness of population replacement strategy. Insight is given into how computational models can provide information on the population dynamics of mosquitoes and the spread of transposable elements through A. gambiae subspecies. The ethical considerations of releasing genetically modified mosquitoes into the wild are discussed. | 18,979,025 |
Structure of lyotropic self-assembled lipid nonlamellar liquid crystals and their nanoparticles in mixtures of phosphatidyl choline and alpha-tocopherol (vitamin E). | The structural/phase behaviour of self-assembled lyotropic liquid crystals formed in mixtures of a phospholipid and alpha-tocopherol (vitamin E) is presented. | 18,979,032 |
Photo-degradation of yperite over V, Fe and Mn-doped titania-silica photocatalysts. | The photocatalytic decomposition of yperite (bis(2-chloroethyl)sulfide), a chemical warfare agent, was achieved by using titania-silica catalysts doped with several transition metal ions. The preparation of these catalysts was achieved by impregnation of a titania-silica mixed oxide previously synthesized using a sol-gel route with salts of the doping elements (vanadium, iron, manganese). The above catalysts were characterized using several spectroscopic techniques: FTIR, Raman, DR-UV-Vis, and XPS. The band gap energy was measured for each photocatalytic system. The reaction was carried out in two different types of reactors, i.e. naturally aerated and a closed quartz tube aerated under a constant flow, and using two types of irradiation, UV-Vis and Vis. The investigated systems proved to be extremely active, leading to an almost complete degradation of yperite in 2 h of irradiation. An excellent correlation between the photocatalytic performances and the band gap has been found. Based on the characterization data and on the temporal evolution of the reaction products, a reaction mechanism has been suggested. This mechanism considers two distinct pathways for the decomposition of yperite, namely the C-S bond cleavage and the S oxidation. | 18,979,041 |
H-Bond interactions between silicates and water during zeolite pre-nucleation. | The relative strength of water-water, water-silicate and silicate-silicate interactions are studied, in order to explain the low solubility of the monomer (Si(OH)(4)), and determine the degree of dispersion of silicate clusters in solution during the hydrothermal synthesis of zeolites. We will show how the hydrogen bond interactions between water and monomeric silicate species are similar to that in pure water, whilst monomer-monomer interactions are stronger. However, when larger silicate species are also considered we find the relative hydrogen-bonding strength to follow: water-water < silicate-water < silicate-silicate. The effects of pH are also considered. The implications of the relative strength of these interactions on the formation of larger silicate species, leading to zeolite pre-nucleation, are discussed. | 18,979,042 |
Contamination profiles of antifouling biocides in selected coastal regions of Malaysia. | The concentrations of butyltins (BTs) in sediment from Peninsular Malaysia along the Strait of Malacca and their spatial distribution are discussed. The concentrations of BTs were high in the southern part of Peninsular Malaysia where there is a lot of ship traffic, because trade is prosperous. The concentrations of monobutyltin (MBT), dibutyltin (DBT), and tributyltin (TBT) in sediment from the coastal waters of Peninsular Malaysia were in the range 4.1-242 microg/kg dry weight (dw), 1.1-186 microg/kg dw, and 0.7-228 microg/kg dw, respectively. A higher percentage of TBT was observed in the area where TBT concentrations were high. The concentrations of monophenyltin (MPT), diphenyltin (DPT), and triphenyltin (TPT) were in the range <0.1-121 microg/kg dw, 0.4-27 microg/kg dw, and 0.1-34 microg/kg dw in sediment from Peninsular Malaysia, respectively. MPT was the dominant phenyltin species. MBT, DBT, and TBT in green mussel (Perna viridis) samples were detected in the range 41-102 microg/kg, 3-5 microg/kg, and 8-32 microg/kg, respectively. A tolerable average residue level (TARL) was estimated at 20.4 microg/kg from a tolerable daily intake (TDI) of 0.25 microg TBTO/kg body weight/day. The maximum value of TBT detected in green mussel samples was the value near the TARL. TPTs were not detected in green mussel samples. The concentrations of Diuron and Irgarol 1051 in sediment from Peninsular Malaysia were in the range <0.1-5 microg/kg dw and <0.1-14 microg/kg dw, respectively. High concentrations of these compounds were observed in locations where the concentrations of TBT were high. Sea Nine 211, Dichlofluanid, and Pyrithiones were not detected in sediment. The concentrations of antifouling biocides in Melaka and the Strait of Johor were investigated in detail. BTs were found in similar concentrations among all sampling sites from Melaka, indicating that BT contamination spread off the coast. However, Sea Nine 211, Diuron, and Irgarol 1051 in the sediment from Melaka were high at the mouth of the river. BT concentrations at the Strait of Johor were higher than those in Peninsular Malaysia and Melaka and were high at the narrowest locations with poor flushing of water. The concentrations of antifouling biocides were compared among Malaysia, Thailand, and Vietnam. A higher concentration and wide variations of TBT and TPT in sediment from Malaysia were observed among these countries. The Irgarol 1051 concentrations in sediment from Malaysia were higher than those in Thailand and Vietnam. | 18,979,060 |
A case report of glomerulopathy-associated podocytic infolding in a patient with tumor lysis syndrome. | A 59-year-old man underwent total gastrectomy and splenectomy for gastric cancer 14 months before admission. The pathological diagnosis was neuroendocrine carcinoma of the stomach. Eight months after the operation, systemic chemotherapy with irinotecan and cisplatin was started because of multiple metastases to lymph nodes. After two courses of chemotherapy, renal function continued to decline. Renal biopsy showed acute tubular necrosis with cast formation, where needle crystallization was found. These clinicopathological findings suggested that tumor lysis syndrome was the cause of acute renal insufficiency. Moreover, diffuse, global bubbling and focal segmental spike formation were revealed by periodic acid-silver methenamine stain in the glomerular basement membrane. Electron microscopy showed an infolding of the cytoplasm of podocytes into the basal basement membrane and spotty electron-lucent areas. These ultrastructural findings, but not epimembranous deposits, corresponded with the bubbling on PAM staining. The present case was a rare case of glomerulopathy associated with podocytic infolding, which was not associated with collagen disease but with tumor lysis syndrome. | 18,979,061 |
Association between polymorphisms in the biometabolism genes CYP1A1, GSTM1, GSTT1 and GSTP1 in bladder cancer. | Numerous enzymes, including Cytochrome P450s (phase I) and Glutathione-S-transferases (phase II), are involved in the metabolic activation and detoxification of carcinogens. Epidemiological studies have consistently demonstrated that bladder cancer is strongly associated with cigarette smoking, and the risk for the development of this neoplasia may be modified by individual differences in carcinogen-metabolizing genes. We investigated the relationship between polymorphisms in the CYP1A1, GSTM1, GSTT1, and GSTP1 genes in a case-control study with 100 bladder cancer patients and 100 controls matched for age, gender, race, and smoking status. The GSTM1, GSTT1, CYP1A1 (A2455-->G), and GSTP1 (A313-->G) genotypes were determined using a multiplex PCR, an allele specific PCR, and a restriction fragment length polymorphism-PCR method. The present case-controlled association study did not detect any positive or negative association for the GSTM1 and GSTP1 genes [odds ratios (OR) = 1.35; 95% confidence interval (CI) = 0.76-2.41 and OR = 0.75; 95% CI = 0.41-1.38, respectively]. Notably, the genes GSTT1 and CYP1A1 exhibited a statistically significant association with bladder cancer (OR = 1.77; 95% CI = 1.01-3.12 and OR = 1.99; 95% CI = 1.07-3.73). No differences for GSTM1 and GSTP1 genotype prevalence between the bladder cancer cases and the controls were observed, however, the null genotype for the GSTT1 gene and the A/G and G/G variants of the CYP1A1 gene may contribute to the development of bladder cancer. | 18,979,064 |
A "bad" case of Tako-Tsubo syndrome. | The prognosis of Tako-Tsubo syndrome (TTS) is believed to be favorable. In most of the cases, there is a complete recovery of left ventricular (LV) function and of symptoms, but previous cases have been described with low-output syndrome, deaths within the first 24 h from acute heart failure, and some deaths due to LV free wall rupture. We describe a case of a patient with TTS who died after right ventricular (RV) free wall rupture. Furthermore, this report suggests that cardiac magnetic resonance imaging with echocardiography might be a useful integrated imaging diagnostic tool for the diagnosis of TTS, ruling out acute coronary syndrome. | 18,979,067 |
Regulator of G-protein signalling expression and function in ovarian cancer cell lines. | Regulator of G-protein signalling (RGS)(2) proteins critically regulate signalling cascades initiated by G-protein coupled receptors (GPCRs) by accelerating the deactivation of heterotrimeric G-proteins. Lysophosphatidic acid (LPA) is the predominant growth factor that drives the progression of ovarian cancer by activating specific GPCRs and G-proteins expressed in ovarian cancer cells. We have recently reported that RGS proteins endogenously expressed in SKOV-3 ovarian cancer cells dramatically attenuate LPA stimulated cell signalling. The goal of this study was twofold: first, to identify candidate RGS proteins expressed in SKOV-3 cells that may account for the reported negative regulation of G-protein signalling, and second, to determine if these RGS protein transcripts are differentially expressed among commonly utilized ovarian cancer cell lines and non-cancerous ovarian cell lines. Reverse transcriptase-PCR was performed to determine transcript expression of 22 major RGS subtypes in RNA isolated from SKOV-3, OVCAR-3 and Caov-3 ovarian cancer cell lines and non-cancerous immortalized ovarian surface epithelial (IOSE) cells. Fifteen RGS transcripts were detected in SKOV-3 cell lines. To compare the relative expression levels in these cell lines, quantitative real time RT-PCR was performed on select transcripts. RGS19/GAIP was expressed at similar levels in all four cell lines, while RGS2 transcript was detected at levels slightly lower in ovarian cancer cells as compared to IOSE cells. RGS4 and RGS6 transcripts were expressed at dramatically different levels in ovarian cancer cell lines as compared to IOSE cells. RGS4 transcript was detected in IOSE at levels several thousand fold higher than its expression level in ovarian cancer cells lines, while RGS6 transcript was expressed fivefold higher in SKOV-3 cells as compared to IOSE cells, and over a thousand fold higher in OVCAR-3 and Caov-3 cells as compared to IOSE cells. Functional studies of RGS 2, 6, and 19/GAIP were performed by measuring their effects on LPA stimulated production of inositol phosphates. In COS-7 cells expressing individual exogenous LPA receptors, RGS2 and RSG19/GAIP attenuated signalling initiated by LPA1, LPA2, or LPA3, while RGS6 only inhibited signalling initiated by LPA2 receptors. In SKOV-3 ovarian cancer cells, RGS2 but not RGS6 or RGS19/GAIP, inhibited LPA stimulated inositol phosphate production. In contrast, in CAOV-3 cells RGS19/GAIP strongly attenuated LPA signalling. Thus, multiple RGS proteins are expressed at significantly different levels in cells derived from cancerous and normal ovarian cells and at least two candidate RGS transcripts have been identified to account for the reported regulation of LPA signalling pathways in ovarian cancer cells. | 18,979,070 |
Endocytosis as a mechanism of regulating natural killer cell function: unique endocytic and trafficking pathway for CD94/NKG2A. | Natural killer (NK) cells are lymphocytes generally recognized as sentinels of the innate immune system due to their inherent capacity to deal with diseased (stressed) cells, including malignant and infected. This ability to recognize many potentially pathogenic situations is due to the expression of a diverse panel of activation receptors. Because NK cell activation triggers an aggressive inflammatory response, it is important to have a means of throttling this response. Hence, NK cells also express a panel of inhibitory receptors that recognize ligands expressed by "normal" cells. Little or nothing is known about the endocytosis and trafficking of NK cell receptors, which are of great relevance to understanding how NK cells maintain the appropriate balance of activating and inhibitory receptors on their cell surface. In this review, we focus on the ITIM-containing inhibitory receptor CD94/NKG2A showing that it is endocytosed by a previously undescribed macropinocytic-like process that may be related to the maintenance of its surface expression. | 18,979,076 |
Protocols in expedited review: tackling the workload of ethics committees. | This paper describes the experience of the Ethics Committee of the Medical University of Vienna, Austria, while managing the workload of clinical study applications. An expedited review process was introduced for initial review of study protocols regarded as minimal risk interventions in March 2004. A total of 504 study protocols were submitted for review in 2003 and this number has increased to 743 in 2007. Two hundred sixty eight studies were classified as minimal risk in 2007 and allocated to a subgroup of the Committee for review. The time to full approval was shorter for these studies as compared to other protocols. Implementation of initial expedited review can improve the performance of an Ethics Committee. A framework to achieve a single opinion for multisite research of minimal risk interventions should be considered to facilitate these low risk studies. | 18,979,085 |
TOO MANY MOUTHS promotes cell fate progression in stomatal development of Arabidopsis stems. | Mutations in TOO MANY MOUTHS (TMM), which encodes a receptor-like protein, cause stomatal patterning defects in Arabidopsis leaves but eliminate stomatal formation in stems. Stomatal development in wild-type and tmm stems was analyzed to define TMM function. Epidermal cells in young tmm stems underwent many asymmetric divisions characteristic of entry into the stomatal pathway. The resulting precursor cells, meristemoids, appropriately expressed cell fate markers such as pTMM:GFP. However, instead of progressing developmentally by forming a guard mother cell, the meristemoids arrested, dedifferentiated, and enlarged. Thus asymmetric divisions are necessary but not sufficient for stomatal formation in stems, and TMM promotes the fate and developmental progression of early precursor cells. Comparable developmental and mature stomatal phenotypes were also found in tmm hypocotyls and in the proximal flower stalk. TMM is also a positive regulator of meristemoid division in leaves suggesting that TMM generally promotes meristemoid activity. Our results are consistent with a model in which TMM interacts with other proteins to modulate precursor cell fate and progression in an organ and domain-specific manner. Finally, the consistent presence of a small number of dedifferentiated meristemoids in mature wild-type stems suggests that precursor cell arrest is a normal feature of Arabidopsis stem development. | 18,979,118 |
Bioremediation of nitroexplosive wastewater by an yeast isolate Pichia sydowiorum MCM Y-3 in fixed film bioreactor. | Nitroexplosives are essential for security and defense of the nation and hence their production continues. Their residues and transformed products, released in the environment are toxic to both terrestrial and aquatic life. This necessitates remediation of wastewaters containing such hazardous chemicals to reduce threat to human health and environment. Bioremediation technologies using microorganisms become the present day choice. High Melting Explosive (HMX) is one of the nitroexplosives produced by nitration of hexamine using ammonium nitrate and acetic anhydride and hence the wastewater bears high concentration of nitrate and acetate. The present investigation describes potential of a soil isolate of yeast Pichia sydowiorum MCM Y-3, for remediation of HMX wastewater in fixed film bioreactor (FFBR). The flask culture studies showed appreciable growth of the organism in HMX wastewater under shake culture condition within 5-6 days of incubation at ambient temperature (28 +/- 2 degrees C). The FFBR process operated in both batch and continuous mode, with Hydraulic Retention Time (HRT) of 1 week resulted in 50-55% removal in nitrate, 70-88% in acetate, 50-66% in COD, and 28-50% in HMX content. Continuous operation of the reactor showed better removal of nitrate as compared to that in the batch operation, while removal of acetate and COD was comparable in both the modes of operation of the reactor. Insertion of baffles in the reactor increased efficiency of the reactor. Thus, FFBR developed with baffles and operated in continuous mode will be beneficial for bioremediation of high nitrate and acetate containing wastewater using the culture of P. sydowiorum. | 18,979,124 |
Identification and characterization of Wolbachia in Solenopsis saevissima fire ants (Hymenoptera: Formicidae) in southeastern Brazil. | The genus Solenopsis appears to have evolved and radiated very rapidly in South America and then spread throughout the rest of the continent. As part of the expansion process, distribution patterns and different degrees of geographic isolation among populations of S. saevissima can be observed. We have investigated the presence of Wolbachia in 52 colonies and 1623 individuals in southeastern Brazil. Detection of Wolbachia infection was based on amplification of the 16S rRNA and wsp genes by polymerase chain reactions. Wolbachia was found in only one of the four locations investigated and it was observed that the populations were polymorphic for infection. The infection level observed increased during the period of screening. In particular, double infection (16SWA and B) increased from 44% in 2005 to 90% in 2006. The A-group of Wolbachia from the wsp sequences was determined by sequencing. However, two variant wsp sequences were detected in Wolbachia present in these populations. The alignment of our sequences with those deposited in GenBank indicated significant differences in relation to homologous sequences. Phylogenetic relationships were inferred using parsimony, and confidence intervals were estimated by bootstrapping. Then the divergence of the Wolbachia of S. saevissima in the populations studied with other variants allowed us to verify that wSS1 and dwSS2 formed a distinct clade within the A-group (>75%). These results can be useful in studies on the dynamics of ant populations. | 18,979,132 |
Postoperative infection and survival in osteosarcoma patients. | The clinical impact of postoperative deep infection on survival remains controversial in osteosarcoma patients. The authors identified 31 osteosarcoma patients that developed a deep infection within 1 year of operation between 1990 and 2003, and compared clinicopathologic characteristics of 31 patients that developed an infection with those of 316 patients that did not. For survival analysis, 62 noninfected patients matched for prognostic factors such as histologic response, tumor size, and location were also selected. In infected patients, although it was not significant due to the small patient numbers, good response to preoperative chemotherapy and a proximal tibial location were frequently observed. No local recurrence developed in infected patients. Five-year overall and metastasis-free survival rates for the 31 infected patients were as high as 89% and 73%, respectively. However, after matching for clinical factors, no survival difference was noted between infected and noninfected patients. Deep infection has a multifaceted effect on patients. However, the present study suggests that the reported positive effect on survival is likely to be related to the clinical characteristics of infected patients rather than an antitumor effect due to the infection. Further investigations are needed to clarify the precise effects of infection. | 18,979,137 |
Expression and clinical significance of cell cycle regulatory proteins in gallbladder and extrahepatic bile duct cancer. | Disruption of cell cycle controls is a pathognomonic feature of all malignant cells. Therefore, we immunohistochemically investigated the relationship between cell cycle regulatory proteins and clinicopathologic features in order to identify the biomarkers related to the outcome of patients with biliary tract cancer (BTC). A cohort of paraffin-embedded specimens were selected from 36 patients, including 18 gallbladder and 18 extrahepatic bile duct cancers, who underwent curative or palliative surgical resection at Korea University Medical Center from June 1998 to December 2004. Tissue microarrays were used to investigate the immunohistochemical staining for p21, p27, p53, cyclin D1, bcl2, and Ki-67. Univariate and multivariate survival analyses were performed to determine the prognostic significance of each protein expression. Absence of p21 expression independently predicted poor outcome in all cases. Well-differentiated tumor was found to be an independent good prognostic factor in gallbladder cancer. Absence of p21 expression and moderately to poorly differentiated tumor were found to be an independent poor prognostic factor in patients with negative for neural invasion. Absence of p21 and bcl2 were found to be an independent poor prognostic factor in patients with no lymph node metastasis. Absence of p21 expression was a significant independent poor prognostic factor in BTC, partly in patients with biologically less aggressive phenotypes. This finding suggests that determination of p21 expression in surgically resected specimens may provide prognostic information in addition to conventional pathologic findings for patients with BTC, especially those who have biologically less aggressive phenotypes. | 18,979,138 |
Improving patient understanding of prescription drug label instructions. | Patient misunderstanding of instructions on prescription drug labels is common and a likely cause of medication error and less effective treatment. To test whether the use of more explicit language to describe dose and frequency of use for prescribed drugs could improve comprehension, especially among patients with limited literacy. Cross-sectional study using in-person, structured interviews. Three hundred and fifty-nine adults waiting for an appointment in two hospital-based primary care clinics and one federally qualified health center in Shreveport, Louisiana; Chicago, Illinois; and New York, New York, respectively. Correct understanding of each of ten label instructions as determined by a blinded panel review of patients' verbatim responses. Patient understanding of prescription label instructions ranged from 53% for the least understood to 89% for the most commonly understood label. Patients were significantly more likely to understand instructions with explicit times periods (i.e., morning) or precise times of day compared to instructions stating times per day (i.e., twice) or hourly intervals (89%, 77%, 61%, and 53%, respectively, p < 0.001). In multivariate analyses, dosage instructions with specific times or time periods were significantly more likely to be understood compared to instructions stating times per day (time periods--adjusted relative risk ratio (ARR) 0.42, 95% Confidence Interval (CI) 0.34-0.52; specific times--ARR 0.60, 95% CI 0.49-0.74). Low and marginal literacy remained statistically significant independent predictors of misinterpreting instructions (low--ARR 2.70, 95% CI 1.81-4.03; marginal--ARR 1.66, 95% CI 1.18-2.32). Use of precise wording on prescription drug label instructions can improve patient comprehension. However, patients with limited literacy were more likely to misinterpret instructions despite use of more explicit language. | 18,979,142 |
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