title stringlengths 0 1.13k | abstract stringlengths 1 15.7k | PMID int64 22 36.5M |
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Analysis and assessment on heavy metal sources in the coastal soils developed from alluvial deposits using multivariate statistical methods. | An investigation on heavy metal sources, i.e., Cu, Zn, Ni, Pb, Cr, and Cd in the coastal soils of Shanghai, China, was conducted using multivariate statistical methods (principal component analysis, clustering analysis, and correlation analysis). All the results of the multivariate analysis showed that: (i) Cu, Ni, Pb, and Cd had anthropogenic sources (e.g., overuse of chemical fertilizers and pesticides, industrial and municipal discharges, animal wastes, sewage irrigation, etc.); (ii) Zn and Cr were associated with parent materials and therefore had natural sources (e.g., the weathering process of parent materials and subsequent pedo-genesis due to the alluvial deposits). The effect of heavy metals in the soils was greatly affected by soil formation, atmospheric deposition, and human activities. These findings provided essential information on the possible sources of heavy metals, which would contribute to the monitoring and assessment process of agricultural soils in worldwide regions. | 18,976,857 |
Epidemiology of invasive pneumococcal disease in the Arabian Peninsula and Egypt. | Invasive pneumococcal disease (IPD) causes considerable morbidity and mortality among children worldwide. This review describes the burden of disease and pneumococcal serotypes/serogroups causing disease in children in the Arabian Peninsula and Egypt identified from a literature search from 1990 to 2007. The incidence of IPD in children aged <or=5 years ranged from 3.4 to 53.5 per 100000. Bacteraemia cases were responsible for 61-100% (children <2 years) of total IPD. Pneumococcal meningitis cases ranged from 3% to 25% (<2 years) and from 7% to 30% (<or=5 years). The most common IPD serotypes/serogroups were 14, 23F, 6B, 19F and 6A (<or=5 years). Circulating serotypes/serogroups causing IPD potentially covered by the 7-valent pneumococcal conjugate vaccine (PCV-7) ranged from 49% to 83% (<2 years) and from 61% to 69% (<or=5 years). Penicillin resistance among invasive isolates ranged from 0% to 78%. Case fatality and morbidity rates for pneumococcal meningitis were 0-22% and 10-62%, respectively. Incidence and morbidity data for meningitis and bacteraemia demonstrate a substantial vaccine-preventable burden of IPD in young children. Standardisation of definitions and development of improved regional surveillance/reporting would enable the region to measure better the impact of prevention strategies for IPD, such as infant-based immunisation programmes. | 18,976,887 |
Do we still need the aminoglycosides? | Since the introduction into clinical practice of the aminoglycoside class of antibiotics, a number of other antimicrobial agents with improved safety profile have entered the market. Studies have failed to demonstrate the superiority of aminoglycoside-containing regimens in a number of infection settings. This has raised doubts regarding the actual clinical utility of aminoglycosides. However, the recent emergence of infections due to Gram-negative bacterial strains with advanced patterns of antimicrobial resistance has prompted physicians to reconsider these 'old' antibacterial agents. This revived interest in the use of aminoglycosides has brought back to light the debate on the two major issues related to these compounds, namely the spectrum of antimicrobial susceptibility and toxicity. Although some of the aminoglycosides retain activity against the majority of Gram-negative clinical bacterial isolates in many parts of the world, the relatively frequent occurrence of nephrotoxicity and ototoxicity during aminoglycoside treatment make physicians reluctant to use these compounds in everyday practice. We believe that recent advances in the understanding of the effect of various dosage schedules of aminoglycosides on toxicity combined with the retained (to a considerable degree) activity against the majority of Gram-negative bacterial isolates make this class of antibiotics still valuable in today's clinical practice. | 18,976,888 |
Genotype-phenotype correlations in ACTA1 mutations that cause congenital myopathies. | Mutations in the skeletal muscle actin gene, ACTA1 are responsible for up to 20% of congenital myopathies with a variety of pathologies that includes nemaline myopathy, intranuclear rod myopathy, actin myopathy and congenital fibre type disproportion. In their review of 2003, Sparrow et al. considered how these actin mutations might affect muscle function at the molecular level and thus cause the disease. Since then several laboratories have taken up the challenge of investigating genotype-phenotype relationships experimentally. The objective of this review is to assess the current state of our understanding of the molecular mechanisms of skeletal myopathies and the prospects for future therapies based on this knowledge. Thirty congenital myopathy-causing ACTA1 mutations have been studied using a range of biochemical and in vitro approaches. They showed diverse molecular defects, and there is no obvious pattern seen in mutations resulting in the same histopathology. | 18,976,909 |
Selective detection of specific protein-ligand complexes by electrosonic spray-precursor ion scan tandem mass spectrometry. | A novel mass spectrometric method for the selective detection of specific protein-ligand complexes is presented. The new method is based on electrosonic spray ionization of samples containing protein and ligand molecules, and mass spectrometric detection using the precursor ion scanning function on a triple quadrupole instrument. Mass-selected intact protein-ligand complex ions are subjected to fragmentation by means of collision-induced dissociation in the collision cell of the instrument, while the second mass analyzer is set to the m/z of protonated ligand ions or their alkali metal adducts. The method allows for the detection of only those ions which yield ions characteristic of the ligand molecules upon fragmentation. Since the scan range of first analyzer is set well above the m/z of the ligand ion, and the CID conditions are established to permit fragmentation of only loosely bound, noncovalent complexes, the method is specific to the detection of protein-ligand complexes under described conditions. Behavior of biologically specific and nonspecific complexes was compared under various instrumental settings. Parameters were optimized to obtain maximal selectivity for specific complexes. Specific and nonspecific complexes were found to show markedly different fragmentation characteristics, which can be a basis for selective detection of complexes with biological relevance. Preparation of specific and nonspecific complexes containing identical building blocks was attempted. Complex ions with identical stoichiometry but different origin showed the expected difference in fragmentation characteristics, which gives direct evidence for the different mechanism of specific versus nonspecific complex ion formation. | 18,976,932 |
Tyrosine-phosphorylation-dependent translocation of the SLAT protein to the immunological synapse is required for NFAT transcription factor activation. | SWAP-70-like adaptor of T cells (SLAT) is a guanine nucleotide exchange factor for Rho GTPases that regulates the development of T helper 1 (Th1) and Th2 cell inflammatory responses by controlling the Ca(2+)-NFAT signaling pathway. However, the mechanism used by SLAT to regulate these events is unknown. Here, we report that the T cell receptor (TCR)-induced translocation of SLAT to the immunological synapse required Lck-mediated phosphorylation of two tyrosine residues located in an immunoreceptor tyrosine-based activation motif-like sequence but was independent of the SLAT PH domain. This subcellular relocalization was coupled to, and necessary for, activation of the NFAT pathway. Furthermore, membrane targeting of the SLAT Dbl-homology (catalytic) domain was sufficient to trigger TCR-mediated NFAT activation and Th1 and Th2 differentiation in a Cdc42-dependent manner. Therefore, tyrosine-phosphorylation-mediated relocalization of SLAT to the site of antigen recognition is required for SLAT to exert its pivotal role in NFAT-dependent CD4(+) T cell differentiation. | 18,976,935 |
The effect of 1alpha,25(OH)2D3 vitamin over oxidative stress and biochemical parameters in rats where Type 1 diabetes is formed by streptozotocin. | The 1alpha,25-dihydroxyvitamin D(3) [1alpha,25(OH)(2)D(3)] plays an essential role in mineral balance but has also been recognized as a powerful modulator of immune response. We aimed to examine the effect of the 1alpha,25(OH)(2)D(3) treatment on insulin/c-peptide, catalase, superoxide dismutase (SOD), and blood glucose in rats that take streptozotocin (STZ). Forty pieces of male rats of Albino family whose average weights were 261.00+/-07.62 g were used in the study. Rats were made diabetic by giving STZ of 40 mg/kg during 5 days through intraperitoneal path. Some of the diabetic group and nondiabetic group were received 1alpha,25(OH)(2)D(3). The levels of SOD, insulin, c-peptide, glucose, SOD, and catalase were measured at the zero, second, fourth, and sixth weeks. Erythrocyte SOD levels didn't show a significant difference at the end of the sixth week in all groups when compared to the beginning. While erythrocyte catalase levels didn't show a significant difference in nondiabetic control and nondiabetic with vitamin D, and diabetic with vitamin D groups at the end of sixth week when compared to the beginning, a significant measurement was made in diabetic without vitamin D group. Maximal insulinitis scoring values were observed in diabetic without vitamin D that didn't receive 1alpha,25(OH)(2)D(3) treatment. The highness of insulin and c-peptide levels in the group that received treatment when compared to other groups and the lowness of oxidative markers such as SOD, catalase in this study can be explained by the fact that 1alpha,25(OH)(2)D(3) treatment prevents the intervention of apoptosis mechanism. | 18,976,933 |
Resonance Rayleigh scattering spectra, non-linear scattering spectra of tetracaine hydrochloride-erythrosin system and its analytical application. | The interaction between erythrosine (ET) and tetracaine hydrochloride (TA) was studied by resonance Rayleigh scattering (RRS), frequency doubling scattering (FDS) and second-order scattering (SOS) combining with absorption spectrum. In a weak acidic medium of Britton-Robinson (BR) buffer solution of pH 4.5, erythrosine reacted with tetracaine hydrochloride to form 1:1 ion-association complex. As a result, the new spectra of RRS, SOS and FDS appeared and their intensities enhanced greatly. The maximum peaks of RRS, SOS and FDS were at 342 nm, 680 nm and 380 nm, respectively. The intensities of the three scattering were directly proportional to the concentration of TA in the range of 0.008-4.2 microg mL(-1) for RRS, 0.027-4.2 microg mL(-1) for SOS and 0.041-4.2 microg mL(-1) for FDS. The methods had very high sensitivities and good selectivities, and the detection limits were 0.003 microg mL(-1) for RRS, 0.008 microg mL(-1) for SOS and 0.012 microg mL(-1) for FDS, respectively. Therefore, a new method was developed to determinate trace amounts of TA. The recovery for the determination of TA in blood serum and urine samples was between 97.0% and 103.8%. In this study, mean polarizability was calculated by AM1 quantum chemistry method. In addition, the reasons for the enhancement of scattering spectra and the energy transfer between absorption, fluorescence and RRS were discussed. | 18,976,950 |
Managing the femoral artery in coronary angiography. | Vascular access and subsequent methods to obtain haemostasis are commonly overlooked components of coronary angiography, yet most complications related to diagnostic coronary angiography and percutaneous coronary interventions come from groin bleeds. Most of these complications are minor, leading to bruising and patient discomfort. However, major vascular complications such as retroperitoneal bleeding are life threatening. A number of devices are now available to ensure the arteriotomy can be closed immediately at the end of the procedure. These devices have advantages but are in themselves the source of additional complications, which are not seen without them. The mechanisms related to the use of these devices and the potential complications that they may cause should be understood by all cardiologists performing coronary angiography. | 18,976,958 |
Treatment-emergent endocrine symptoms and the risk of breast cancer recurrence: a retrospective analysis of the ATAC trial. | When the mechanism of action behind treatment toxicity reflects the intended effect on the treatment target, the toxicity might be a useful marker for efficacy. During endocrine treatment of breast cancer, the occurrence of symptoms related to oestrogen depletion or oestrogen blockade might thus be a predictor of treatment effectiveness. In this retrospective analysis, the relation between the reported incidence of vasomotor or joint symptoms and breast cancer recurrence in the Arimidex, Tamoxifen, Alone or in Combination (ATAC) trial is assessed. Women with hormone-receptor-positive tumours who reported vasomotor or joint symptoms at the first follow-up visit (3 months) in the ATAC trial, (which assessed tamoxifen or anastrozole for adjuvant treatment of postmenopausal breast cancer), were compared with women without these symptoms to see if there was a relation between these symptoms and subsequent recurrence. The ATAC trial is registered as an International Standard Randomised Controlled Trial, number ISRCTN18233230. 1486 of 3964 (37.5%) eligible women reported newly emergent vasomotor symptoms at the 3-month follow-up visit and had lower subsequent recurrence than those who did not report these symptoms (223 during 10 752 women-years of follow-up vs 366 during 11 573 woman-years of follow-up, respectively; hazard ratio [HR] 0.84 [95% CI 0.71-1.00], p=0.04; adjusted for age, body-mass index, previous hormone-replacement therapy, nodal status, tumour size, and tumour grade). A greater decrease in breast-cancer recurrence was seen for the 1245 of 3964 (31.4%) eligible women who reported new joint symptoms at the 3-month follow-up visit compared with those not reporting these symptoms (158 during 9242 women-years of follow-up vs 366 during 11 573 women-years of follow-up; adjusted HR 0.60 [0.50-0.72], p<0.0001). The appearance of new vasomotor symptoms or joint symptoms within the first 3 months of treatment is a useful biomarker, suggesting a greater response to endocrine treatment compared with women without these symptoms. Awareness of the relation between early treatment-emergent symptoms and beneficial response to therapy might be useful when reassuring patients who present with them, and might help to improve long-term treatment adherence when symptoms cannot be alleviated effectively. | 18,976,959 |
A single-blind, placebo run-in study of duloxetine for activity-limiting osteoarthritis pain. | Osteoarthritis pain is a significant problem for our aging population. Antidepressants that are serotonin-norepinephrine reuptake inhibitors are effective for other forms of chronic pain and may provide a new treatment option for osteoarthritis pain. We performed a single-blind, placebo run-in trial of 60 to 90 mg of duloxetine in 25 subjects with activity-limiting osteoarthritis pain. Each subject received 2 weeks of placebo followed by 10 weeks of duloxetine. The primary outcome was reduction in average pain intensity between 2 and 12 weeks for subjects completing the trial. Average pain on the Brief Pain Inventory (BPI) was 5.7 at baseline, 4.8 after the 2-week placebo run-in, and 3.5 at 12 weeks for the 17 patients completing the trial (28% decrease between 2 and 12 weeks, P = .122). Eight of 15 study completers who had nonmissing BPI results (53%) reported at least 30% pain reduction between weeks 2 and 12. The Western Ontario McMaster Osteoarthritis Index (WOMAC) pain score at baseline was 2.3, 1.8 after 2 weeks, and 1.3 after 12 weeks (30% decrease between 2 and 12 weeks, P = .018). Ten of 17 patients (59%) reported at least 30% pain relief between weeks 2 and 12 on the WOMAC. Significant improvements in self-reported physical and role function were reported but observed physical function did not improve. Duloxetine did not significantly reduce pain intensity on the BPI but did improve pain intensity and self-reported function on the WOMAC. Duloxetine warrants further investigation as a novel treatment for osteoarthritis pain. | 18,976,962 |
A prolonged nitric oxide-dependent, opioid-mediated antinociceptive effect of hyperbaric oxygen in mice. | Hyperbaric oxygen (HBO(2)) therapy is reported to cause pain relief in several conditions of chronic pain. A single 60-minute session of HBO(2) treatment produced a prolonged antinociceptive effect in mice that persisted for 90 minutes after cessation of treatment. The HBO(2)-induced antinociception was significantly attenuated by pretreatment before HBO(2) exposure with the opioid antagonist naltrexone, the nonspecific nitric oxide synthase (NOS)-inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME), and the selective neuronal NOS-inhibitor S-methyl-L-thiocitrulline (SMTC) but not the selective endothelial NOS-inhibitor N(5)-(1-iminoethyl)-L-ornithine (L-NIO). The antinociception was also significantly reduced by central pretreatment with a rabbit antiserum against dynorphin(1-13) but not by rabbit antisera against either beta-endorphin or methionine-enkephalin. The prolonged antinociceptive effect at 90 minutes after HBO(2)-induced treatment was also significantly attenuated by naltrexone but not L-NAME administered 60 minutes after HBO(2) treatment but before nociceptive testing. These findings indicate that the antinociception that persists for 90 minutes after HBO(2) exposure is mediated by nitric oxide (NO) and opioid mechanisms but that the NO involvement is critical during the HBO(2) treatment and not at the time of nociceptive testing. These results are consistent with the concept that HBO(2) may induce an NO-dependent release of opioid peptide to cause a long-acting antinociceptive effect. This article presents evidence of a persistent antinociceptive effect of hyperbaric oxygen treatment that is mediated by opioid and NO mechanisms. Further elucidation of the underlying mechanism could identify molecular targets to cause a longer-acting activation of endogenous pain-modulating systems. | 18,976,963 |
Modelling of mandibular movement. | In this paper, the authors presented a novel method to reconstruct individual mandible movement in three dimensions by a virtual articulator system. The system provides a synchronized 3D mandibular movement that faithfully reappear one's natural occlusion movements--sagittal border, lateral, and open-close movements. Movement trajectories are approximated by cubic or high-degree curves modelling. During the whole process, X-ray exposure on human is avoided. The authors apply the optimal methodology to approach the collected samples of movements in order to generate specific occlusion curves and surfaces. The system provides a novel method of mimicking occlusion of individuals. It is a useful tool for recording dynamic movements of an individual in both pre- and post-surgery and also for predicting surgical outcomes. | 18,976,989 |
Preparative separation of a terpenoid and alkaloids from Tripterygium wilfordii Hook. f. using high-performance counter-current chromatography. Comparison of various elution and operating strategies. | This paper describes how high-performance counter-current chromatography (HPCCC) was used strategically for the separation of Tripterygium wilfordii Hook. f. Due to the complexity of Chinese herbal medicines, the initial ethanol crude extract was fractionated into seven fractions using medium-pressure liquid chromatography (MPLC). One terpenoid (triptolide) and three alkaloids (peritassine A, wilforgine and wilforine) were further separated from one of the MPLC fractions. This fraction (1.25 g) yielded 8 mg of triptolide and 28 mg of peritassines A after one HPCCC column pass and 30 mg of wilforgine and 120 mg of wilforine after a second column pass with respective purities of 97%, 93.6%, 95.0% and 94.4%, which were determined by high-performance liquid chromatography (HPLC). This was a one-step HPCCC separation, using an n-hexane-ethyl acetate-methanol-water (4:5:4:5, v/v) solvent system, where increases in theoretical plates have been sacrificed in favour of increasing throughput. Structures were identified by electrospray ionization mass spectrometry (ESI-MS), (1)H nuclear magnetic resonance ((1)H NMR) and (13)C nuclear magnetic resonance ((13)C NMR). Comparison of three different modes of eluting compounds retained in the liquid stationary phase: elution extrusion; dual mode and simple pump-out showed that simply pumping out the column contents at high flow gave better resolution and was eight times faster than the other two well-utilised methods. Triptolide and peritassines A were isolated for the first time from Tripterygium wilfordii Hook. f. | 18,976,997 |
Oxidation of volatile organic compounds on SBA-15 mesoporous molecular sieves modified with manganese. | Catalytic combustion of volatile organic compounds, such as propene, has been studied on manganese modified mesoporous molecular sieves. Powder X-ray diffraction, (29)Si nuclear magnetic resonance, nitrogen sorption and transmission electron microscopy show that the SBA-15 mesoporous silica molecular sieve can be modified with manganese using Mn(2)(CO)(10) or Mn(O(2)CMe)(2) without significant distortion of the host structure. The two products were catalytically active in propene oxidation, with SBA-15 modified with Mn(2)(CO)(10) showing significantly higher activity, possibly due to higher Mn content, than SBA-15 modified with Mn(O(2)CMe)(2). | 18,977,012 |
Salivary cortisol in unaffected twins discordant for affective disorder. | Dysfunction in the hypothalamic-pituitary-adrenal (HPA) axis has been proposed as a biological endophenotype for affective disorders. In the present study the hypothesis that a high genetic liability to affective disorder is associated with higher cortisol levels was tested in a cross-sectional high-risk study. Healthy monozygotic (MZ) and dizygotic (DZ) twins with (High-Risk twins) and without (Low-Risk twins) a co-twin history of affective disorder were identified through nationwide registers. Awakening and evening salivary cortisol levels were compared between the 190 High- and Low-Risk twins. The 109 High-Risk twins had significantly higher evening cortisol levels than the 81 Low-Risk MZ twins, also after adjustment for age, sex, and the level of subclinical depressive symptoms. No significant difference was found in awakening cortisol levels between High-Risk and Low-Risk twins. In conclusion, a high genetic liability to affective disorder was associated with a higher evening cortisol level, but not with awakening cortisol level. Future prospective family, high-risk and twin studies are needed to decide whether abnormalities in the HPA axis can be identified as an endophenotype of affective disorder. | 18,977,033 |
Impact of stress and mast cells on brain metastases. | Metastases continue to be the chief cause of morbidity and mortality for many tumors, including brain metastases of lung and mammary adenocarcinoma. Stress appears to increase metastases, but the mechanism is not understood. Recent evidence suggests that local inflammation is conducive for cancer growth and a unique immune cell, the mast cell, accumulates in the stroma surrounding tumors and is critically located at the blood-brain-barrier (BBB). Mast cells express receptors for and can be stimulated by corticotropin-releasing hormone (CRH), secreted under stress, to release mediators such as histamine, IL-8, tryptase and vascular endothelial growth factor (VEGF), which disrupt the BBB permitting metastases. Stress and mast cells could serve as new targets for drug development to prevent brain metastases, especially since CRH receptor antagonists and brain mast cell inhibitors have recently been developed. | 18,977,036 |
PrP antibody binding-induced epitope modulation evokes immunocooperativity. | We have characterized the antibody-antigen binding events of the prion protein (PrP) utilizing three new PrP-specific monoclonal antibodies (Mabs). The degree of immunoreactivity was dependent on the denaturation treatment with the combination of heat and SDS resulting in the highest levels of epitope accessibility and antibody binding. Interestingly however, this harsh denaturation treatment was not sufficient to completely and irreversibly abolish protein conformation. The Mabs differed in their PrP epitopes with Mab 08-1/11F12 binding in the region of PrP(93-122), Mab 08-1/8E9 reacting to PrP(155-200) and Mab 08-1/5D6 directed to an undefined conformational epitope. Using normal and infected brains from hamsters, sheep and deer, we demonstrate that the binding of PrP to one Mab triggers PrP epitope unmasking, which enhances the binding of a second Mab. This phenomenon, termed positive immunocooperativity, is specific regarding epitope and the sequence of binding events. Positive immunocooperativity will likely increase immunoassay sensitivity since assay conditions for PrP(Sc) detection does not require protease digestion. | 18,977,037 |
Osteoporosis and congestive heart failure (CHF) in the elderly patient: double disease burden. | The present study aimed to evaluate the association between osteoporosis and CHF in elderly patients and to assess the effect of physical performance, vitamin D levels, inflammatory markers on this association. One hundred and twenty-six consecutive patients aged 65 years and above, with moderate to severe CHF who presented to our institution for CHF management and 54 age- and sex-matched controls were screened for osteoporosis. All patients were thoroughly interrogated for cause of CHF, medications, smoking, alcohol use, additional comorbidities and previous falls/fractures. A physical examination was performed to assess CHF severity and New York Heart Association (NYHA) class. Bone mineral density (BMD) measurements using dual-energy X-ray absorptiometry (DXA) were performed at the lumbar spine (LS) and femoral neck (FN). Physical performance assessment included grip strength, 6-min walk, "Get up and Go Test", activities of daily living (ADL) and frailty assessment. Biochemical assessment included measurement of levels of serum calcium, phosphorus, 1,25-dihyroxycholecalciferol=1,25(OH)(2)D (vitamin D(3)) and tumor necrosis factor-alpha (TNF-alpha). The BMD-Z-scores were significantly lower in HF patients compared to the non-HF controls. Furthermore, there was an association between the ejection fraction (EF) and the BMD-Z-scores. HF patients were significantly more likely to have poor physical performance, a higher frailty composite score, higher TNF-alpha and lower 1,25(OH)(2)D levels. A significant association was found between EF and frailty score, p<0.001. The results suggest that there is an association between HF and lower BMD. The increased bone loss in conjunction with CHF is likely to increase fracture risk. Thus, strategies for optimal treatment of CHF and for optimizing vitamin D(3), calcium and physical activity to improve quality of life (QoL) in these patients who have double disease burden are critical in these individuals. | 18,977,041 |
Engineering microbes with synthetic biology frameworks. | Typically, the outcome of biologically engineered unit operations cannot be controlled a priori due to the incorporation of ad hoc design into complex natural systems. To mitigate this problem, synthetic biology presents a systematic approach to standardizing biological components for the purpose of increasing their programmability and robustness when assembled with the aim to achieve novel biological functions. A complex engineered biological system using only standardized biological components is yet to exist. Nevertheless, current attempts to create and to implement modular, standardized biological components pave the way for the future creation of highly predictable artificial biological systems. Although synthetic biology frameworks can be applied to any biological engineering endeavor, this article will focus on providing a brief overview of advances in the field and its recent utilization for the engineering of microbes. | 18,977,048 |
Is the crime drop of the 1990s in Canada and the USA associated with a general decline in risky and health-related behavior? | Crime rates dropped unexpectedly and dramatically in the 1990s in Canada and the USA. The decline was not restricted to particular types of crime, the particular methodologies of crime reports, demographic characteristics, or geographical areas. Psychological studies of individuals have suggested a link between crime and different types of risky behavior (e.g., dangerous driving, unsafe sex, substance use). Based on this link, we examined whether national rates of various risky behaviors declined in the 1990s, and whether rates of crime and risky behavior covary over time. Several American and Canadian databases reporting annual or biennial data on risky behavior indicators were examined. Results indicate that most of the risky behavior indicators in the domains of violent behavior, accidents, sexual behavior, and school dropout declined in the 1990s. Furthermore, time series analyses suggest that rates of various risky behaviors tend to covary with homicide over long periods of time. An important exception to these results is substance use in various contexts. We discuss some theoretical implications of the results. | 18,977,063 |
Motexafin gadolinium combined with prompt whole brain radiotherapy prolongs time to neurologic progression in non-small-cell lung cancer patients with brain metastases: results of a phase III trial. | To determine the efficacy of motexafin gadolinium (MGd) in combination with whole brain radiotherapy (WBRT) for the treatment of brain metastases from non-small-cell lung cancer. In an international, randomized, Phase III study, patients with brain metastases from non-small-cell lung cancer were randomized to WBRT with or without MGd. The primary endpoint was the interval to neurologic progression, determined by a centralized Events Review Committee who was unaware of the treatment the patients had received. Of 554 patients, 275 were randomized to WBRT and 279 to WBRT+MGd. Treatment with MGd was well tolerated, and 92% of the intended doses were administered. The most common MGd-related Grade 3+ adverse events included liver function abnormalities (5.5%), asthenia (4.0%), and hypertension (4%). MGd improved the interval to neurologic progression compared with WBRT alone (15 vs. 10 months; p = 0.12, hazard ratio [HR] = 0.78) and the interval to neurocognitive progression (p = 0.057, HR = 0.78). The WBRT patients required more salvage brain surgery or radiosurgery than did the WBRT+MGd patients (54 vs. 25 salvage procedures, p < 0.001). A statistically significant interaction between the geographic region and MGd treatment effect (which was in the prespecified analysis plan) and between treatment delay and MGd treatment effect was found. In North American patients, where treatment was more prompt, a statistically significant prolongation of the interval to neurologic progression, from 8.8 months for WBRT to 24.2 months for WBRT+MGd (p = 0.004, HR = 0.53), and the interval to neurocognitive progression (p = 0.06, HR = 0.73) were observed. In the intent-to-treat analysis, MGd exhibited a favorable trend in neurologic outcomes. MGd significantly prolonged the interval to neurologic progression in non-small-cell lung cancer patients with brain metastases receiving prompt WBRT. The toxicity was acceptable. | 18,977,094 |
Dose-response relationship for image-guided stereotactic body radiotherapy of pulmonary tumors: relevance of 4D dose calculation. | To evaluate outcome after image-guided stereotactic body radiotherapy (SBRT) for early-stage non-small-cell lung cancer (NSCLC) and pulmonary metastases. A total of 124 patients with 159 pulmonary lesions (metastases n = 118; NSCLC, n = 41; Stage IA, n = 13; Stage IB, n = 19; T3N0, n = 9) were treated with SBRT. Patients were treated with hypofractionated schemata (one to eight fractions of 6-26 Gy); biologic effective doses (BED) to the clinical target volume (CTV) were calculated based on four-dimensional (4D) dose calculation. The position of the pulmonary target was verified using volume imaging before all treatments. With mean/median follow-up of 18/14 months, actuarial local control was 83% at 36 months with no difference between NSCLC and metastases. The dose to the CTV based on 4D dose calculation was closely correlated with local control: local control rates were 89% and 62% at 36 months for >100 Gy and <100 Gy BED (p = 0.0001), respectively. Actuarial freedom from regional and systemic progression was 34% at 36 months for primary NSCLC group; crude rate of regional failure was 15%. Three-year overall survival was 37% for primary NSCLC and 16% for metastases; no dose-response relationship for survival was observed. Exacerbation of comorbidities was the most frequent cause of death for primary NSCLC. Doses of >100 Gy BED to the CTV based on 4D dose calculation resulted in excellent local control rates. This cutoff dose is not specific to the treatment technique and protocol of our study and may serve as a general recommendation. | 18,977,095 |
Implanted cardiac defibrillator care in radiation oncology patient population. | To review the experience of a large cancer center with radiotherapy (RT) patients bearing implantable cardiac defibrillators (ICDs) to propose some preliminary care guidelines as we learn more about the devices and their interaction with the therapeutic radiation environment. We collected data on patients with implanted ICDs treated with RT during a 2.5-year period at any of the five Memorial Sloan-Kettering clinical campuses. Information regarding the model, location, and dose detected from the device, as well as the treatment fields, fraction size, and treatment energy was collected. During this time, a new management policy for these patients had been implemented requiring treatment with low-energy beams (6 MV) and close surveillance of the patients in partnership with their electrophysiologist, as they received RT. During the study period, 33 patients were treated with an ICD in place. One patient experienced a default of the device to its initial factory setting that was detected by the patient hearing an auditory signal from the device. This patient had initially been treated with a 15-MV beam. After this episode, his treatment was replanned to be completed with 6-MV photons, and he experienced no further events. Patients with ICDs and other implanted computer-controlled devices will be encountered more frequently in the RT department, and proper management is important. We present a policy for the safe treatment of these patients in the radiation oncology environment. | 18,977,096 |
Simultaneous determination of jujuboside A, B and betulinic acid in semen Ziziphi spinosae by high performance liquid chromatography-evaporative light scattering detection. | A reverse phase high performance liquid chromatographic (HPLC) method with evaporative light scattering detection (ELSD) was developed for simultaneous determination of jujuboside A, B and betulinic acid in semen Ziziphi spinosae. The analysis was performed by gradient elution, using an aqueous mobile phase (containing 0.1% acetic acid) modified by acetonitrile. The evaporator tube temperature of ELSD was set at 45 degrees C, and with the nebulizing gas flow-rate of 1.8l/min. The method was validated for accuracy, reproducibility, precision and limits of detection and quantification. Quantification of the three active compounds in semen Ziziphi spinosae from different locations was performed by this method, which provides a new tool for quality assessment of semen Ziziphi spinosae. | 18,977,107 |
Dopamine antagonism inhibits anorectic behavior in an animal model for anorexia nervosa. | Excessive physical activity is commonly described as symptom of Anorexia Nervosa (AN). Activity-based anorexia (ABA) is considered an animal model for AN. The ABA model mimics severe body weight loss and increased physical activity. Suppression of hyperactivity by olanzapine in anorectic patients as well as in ABA rats suggested a role of dopamine and/or serotonin in this trait. Here, we investigated the effect of a non-selective dopamine antagonist in the ABA model. A dose-response curve of chronic treatment with the non-selective dopaminergic antagonist cis-flupenthixol was determined in the ABA model. Treatment reduced activity levels in both ad libitum fed and food-restricted rats. Treated ABA rats reduced body weight loss and increased food intake. These data support a role for dopamine in anorexia associated hyperactivity. Interestingly, in contrast to leptin treatment, food-anticipatory activity still persists in treated ABA rats. | 18,977,121 |
Risk assessment of pneumothorax and pulmonary haemorrhage complicating percutaneous co-axial cutting needle lung biopsy. | The primary aim of this study was to evaluate the ability of radiologists to accurately estimate pneumothorax and pulmonary haemorrhage during percutaneous co-axial cutting needle CT-guided lung biopsy. Patients undergoing cutting needle lung biopsy during the study period were identified; the path taken by the cutting needle marked on each pre-biopsy staging CT scan. Each scan was then reviewed independently by two thoracic radiologists blinded to clinical details and complications; pneumothorax and pulmonary haemorrhage risk estimated with a percentage Visual Analogue Scale. In 134 patients, pneumothorax occurred in 24%. The radiologists differed in the estimation of pneumothorax risk in 55% (74 episodes). When pneumothorax risk was estimated <20% by radiologists 1 and 2, 16% and 14% of biopsies resulted in pneumothorax; where risk was estimated at 20-49%, pneumothorax incidence rose to 33% and 31%; where risk was deemed > or =50%, pneumothorax rate was 87% and 100%. Pulmonary haemorrhage occurred in 4%; estimated haemorrhage risk for biopsies complicated by haemorrhage did not differ significantly from where haemorrhage did not occur. Radiologists differ markedly in the estimation of pneumothorax risk for a patient undergoing co-axial lung biopsy. Identifying individual patients developing pneumothorax was only possible when risk was estimated at > or =50%. Pulmonary haemorrhage was uncommon and difficult to predict accurately. | 18,977,128 |
Rethinking our understanding of the pathogenesis of necrotic enteritis in chickens. | For decades, low doses of antibiotics have been used widely in animal production to promote growth. However, there is a trend to reduce this use of antibiotics in feedstuffs, and legislation is now in place in Europe to prohibit their use in this way. As a consequence, economically important diseases, such as necrotic enteritis (NE) of chickens, that are caused by Clostridium perfringens have become more prevalent. Recent research is creating a paradigm shift in our understanding of the pathogenesis of NE and is now providing information that will be necessary to monitor and control the incidence of NE in poultry. | 18,977,143 |
Gabapentin reverses microglial activation in the spinal cord of streptozotocin-induced diabetic rats. | Diabetes mellitus is the leading cause of peripheral neuropathy worldwide. Despite this high level of incidence, underlying mechanisms of the development and maintenance of neuropathic pain are still poorly understood. Evidence supports a prominent role of glial cells in neuropathic pain states. Gabapentin is used clinically and shows some efficacy in the treatment of neuropathic pain. Here we investigate the distribution and activation of spinal microglia and astrocytes in streptozotocin (STZ)-diabetic rats and the effect of the gold standard analgesic, Gabapentin, on these cells. Mechanical allodynia was observed in four week-diabetic rats. Oral administration of Gabapentin significantly attenuated mechanical allodynia. Quantification of cell markers Iba-1 for microglia and GFAP for astrocytes revealed extensive activation of microglia in the dorsal horn of diabetic rats, whereas a reduction in the number of astrocytes could be observed. In addition, an attenuation of microglial activation correlated with reduced allodynia following Gabapentin treatment, while Gabapentin had no effect on the number of astrocytes. Here we show a role of microglia in STZ-induced mechanical allodynia and furthermore, that the anti-allodynic effect of Gabapentin may be linked to a reduction of spinal microglial activation. Astrocytic activation in this model appears to be limited and is unaffected by Gabapentin treatment. Consequently, spinal microglial activation is a key mechanism underlying diabetic neuropathy. Furthermore, we suggest that Gabapentin may exert its anti-allodynic actions partially through alterations of microglial cell function. | 18,977,160 |
NGX-4010, a high-concentration capsaicin patch, for the treatment of postherpetic neuralgia: a randomised, double-blind study. | The limitations of current treatments for postherpetic neuralgia (PHN) have led to the investigation of localised, non-systemic alternatives. NGX-4010, a high-concentration (8%) capsaicin dermal patch, was developed to treat patients with neuropathic pain. We report the results of a randomised, double blind, 12-week study of the efficacy and safety of one application of NGX-4010 in patients with PHN. In this multicentre, double-blind, parallel-group trial, 402 patients were randomly assigned to one 60-min application of NGX-4010 (640 microg/cm(2) [8% capsaicin]) or a low-concentration capsaicin control patch (3.2 microg/cm(2) [0.04% capsaicin]). Patients were aged 18-90 years, had had postherpetic neuralgia for at least 6 months, and had an average baseline numeric pain rating scale (NPRS) score of 3 to 9. The primary efficacy endpoint was percentage change in NPRS score from baseline to weeks two to eight. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00115310. Patients who were randomly assigned to NGX-4010 (n=206) had a significantly greater reduction in pain during weeks two to eight than did patients who had the control patch (n=196). The mean changes in NPRS score were -29.6%vs -19.9% (difference -9.7%, 95% CI -15.47 to -3.95; p=0.001). 87 (42%) patients who received NGX-4010 and 63 (32%) controls had a 30% or greater reduction in mean NPRS score (odds ratio [OR] 1.56, 95% CI 1.03 to 2.37; p=0.03). The patients who had NGX-4010 had significant improvements in pain during weeks two to 12 (mean change in NPRS score -29.9%vs -20.4%, difference -9.5, -15.39 to -3.61; p=0.002). Transient blood pressure changes associated with changes in pain level were recorded on the day of treatment, and short-lasting erythema and pain at the site of application were common, self-limited, and generally mild to moderate in the NGX-4010 group and less frequent and severe in the controls. One 60-min application of NGX-4010 provided rapid and sustained pain relief in patients with postherpetic neuralgia. No adverse events were associated with treatment except for local reactions at the site of application and those related to treatment-associated pain. | 18,977,178 |
Identification of differentially displayed proteins in cerebrospinal fluid of Parkinson's disease patients: a proteomic approach. | Clinical proteomics has been widely used to identify differentially displayed proteins in blood and cerebrospinal fluid (CSF) to understand the molecular and cellular events leading to Parkinson's disease (PD). The close connection between CSF and the brain offers reliable and reproducible way to assess the majority of changes in the brain proteome profile directly into CSF throughout the course of neurodegeneration. We identified the differentially displayed proteins in CSF of PD patients as compared with controls using two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) and mass spectrometry. Comparative 2-D PAGE electrophoretograms of CSF of PD patients with case controls and/or neurological controls revealed significant differential display of six protein spots. The differentially displayed proteins were identified as serum albumin precursor, serum albumin chain-A, hemoglobin beta fragment, mutant globin, proline rich repeat 14 (PRR 14) and serum transferrin N-terminal lobe. Although the level of hemoglobin beta fragment and mutant globin was attenuated, serum albumin precursor, serum albumin chain-A, PRR 14 and serum transferrin N-terminal lobe were augmented in PD patients as compared with case controls. The level of serum albumin chain-A, PRR 14 and serum transferrin N-terminal lobe was not significantly altered when compared with neurological controls. The results obtained thus suggest that differential display of CSF serum albumin precursor, serum albumin chain-A, PRR 14 and serum transferrin N-terminal lobe could be associated with neuronal dysfunction and hemoglobin/globin with the onset/progression of PD in humans. | 18,977,210 |
3-D measurement of osmotic dehydration of isolated and adhered PC-3 cells. | Cell dehydration during freezing results from an elevated concentration of electrolytes in the extracellular medium that is deeply involved in cellular injury. We undertook real-time threedimensional (3-D) observation of osmotic dehydration of cells, motivated by a comparison of cellular responses between isolated cells in suspension and cultured cells adhering to a surface since several studies have suggested a difference in freeze tolerance between cell suspensions and monolayers. A laser confocal scanner was used with a perfusion microscope to capture sectional images of chloromethylbenzamido (DiI)-stained PC-3 cells that were exposed to an increase in NaCl concentration from 0.15 to 0.5M at 23 degrees C. Change in cell volume was determined from reconstructed 3-D images taken every 2.5s. When cells were exposed to an elevated NaCl concentration, isolated cells contracted and markedly distorted from their original spherical shape. In contrast, adhered cells showed only a reduction in height and kept their basal area constant. Apparent membrane hydraulic conductivity did not vary considerably between isolated and adhered cells, suggesting a negligible effect of the cytoskeletal structure on the rate of water transport. The surface area that contributed to water transport in adhered PC-3 cells was nearly equal to or slightly smaller than that present in isolated cells. Therefore, the similarity in properties and dimensions between isolated and adhered cells indicate that there will be similar extents of dehydration, resulting in a similar degree of supercooling during freezing. | 18,977,212 |
Functional characterisation of hemokinin-1 in mouse uterus. | The preprotachykinin gene Tac4 expressed in murine uterus and placenta is thought to encode a peptide RSRTRQFYGLM-NH(2), mouse hemokinin 1. We have examined the uterotonic effects of mouse hemokinin 1 and its N-terminally truncated analogue, mouse hemokinin 1(2-11) on mouse uterus. Mouse hemokinin 1(2-11) was equieffective with but slightly less potent than substance P in tissues from non-pregnant Swiss mice. On myometrium from Balb C mice primed with oestrogen the positions of concentration-response curves to substance P and the mouse hemokinins were similar to those of neurokinin A, but the maximum responses were lower. The tachykinin NK(1) receptor antagonist, 1-{2-(3, 4-dichlorophenyl)-1-(3-isopropoxyphenylacetyl) piperidin-3-yl]ethyl}-4phenyl-1-azonia-bicyclo[2.2.2]octane (SR 140333), reduced the effects of the agonists in tissues from both groups of mice. In myometria from late pregnant (Days 17-18) Balb C mice the responses to mouse hemokinin 1(2-11) were less potent than in those from oestrogen-primed mice. Human hemokinin 1, the human orthologue of mouse hemokinin 1, was more effective than mouse hemokinin 1(2-11), while endokinin D was inactive. Mouse hemokinin 1 effects were blocked by SR 140333 alone and in combination with ((S)-N-methyl-N[4-acetylamino-4-phenylpiperidino)-2-(3,4-dichlorophenyl)butyl]benzamide (SR 48968) but not by SR 48968 alone. Thus the mouse hemokinins are tachykinin NK(1) receptor-preferring uterotonic agonists in non-pregnant mice but lack action at the myometrial tachykinin NK(2) receptors present in late pregnant mice. | 18,977,217 |
Immediate short-duration hypothermia provides long-term protection in an in vivo model of traumatic axonal injury. | A prospective, multicenter, randomized trial did not demonstrate improved outcomes in severe traumatic brain injured patients treated with mild hypothermia [Clifton, G.L., Miller, E.R., Choi, S.C., Levin, H.S., McCauley, S., Smith, K.R., Jr., Muizelaar, J.P., Wagner, F.C., Jr., Marion, D.W., Luerssen, T.G., Chesnut, R.M., Schwartz, M., 2001. Lack of effect of induction of hypothermia after acute brain injury. N. Engl. J. Med. 344, 556-563.]. However, the mean time to target temperature was over 8 h and patient inclusion was based on Glasgow Coma Scale score so brain pathology was likely diverse. There remains significant interest in the benefits of hypothermia after traumatic brain injury (TBI) and, in particular, traumatic axonal injury (TAI), which is believed to significantly contribute to morbidity and mortality of TBI patients. The long-term beneficial effect of mild hypothermia on TAI has not been established. To address this issue, we developed an in vivo rat optic nerve stretch model of TAI. Adult male Sprague-Dawley rats underwent unilateral optic nerve stretch at 6, 7 or 8 mm piston displacement. The increased number of axonal swellings and bulbs immunopositive for non-phosphorylated neurofilament (SMI-32) seen four days after injury was statistically significant after 8 mm displacement. Ultrastructural analysis 2 weeks after 8 mm displacement revealed a 45.0% decrease (p<0.0001) in myelinated axonal density in the optic nerve core. There was loss of axons regardless of axon size. Immediate post-injury hypothermia (32 degrees C) for 3 h reduced axonal degeneration in the core (p=0.027). There was no differential protection based on axon size. These results support further clinical investigation of temporally optimized therapeutic hypothermia after traumatic brain injury. | 18,977,220 |
Autonomic and cardiovascular effects of central neuromedin U in rats. | Previous studies have demonstrated that neuromedin U (NMU) affects cardiovascular functions such as blood pressure (BP) or heart rate (HR) in rats. Here, we examined the effects of the lateral cerebral ventricular (ICV) injection of various doses of NMU on renal sympathetic nerve activity (RSNA) and BP in urethane-anesthetized rats. ICV injection of NMU elevated RSNA, BP and HR in a dose-dependent manner. Moreover, neither ICV pretreatment of thioperamide, an antagonist of histaminergic H3-receptor, or of diphenhydramine, an antagonist of histaminergic H1-receptor, abolished increasing effects of NMU on RSNA, BP and HR In addition, ICV injection of NMU suppressed gastric vagal nerve activity (GVNA) and activated brown adipose tissue sympathetic nerve activity (BAT-SNA) of anesthetized rats, and elevated brown adipose tissue temperature (BAT-T) of conscious rats. Thus, these evidence suggest that NMU affects neural activities of autonomic nerves containing RSNA, GVNA or BAT-SNA, and BP by mediating central mechanism. | 18,977,236 |
A tailored Internet-plus-email intervention for increasing physical activity among ethnically-diverse women. | To evaluate the feasibility and efficacy of an individually tailored, Internet-plus-email physical activity intervention designed for adult women. Healthy and ethnically-diverse adult females (N=156) (mean age=42.8 years, 65% Caucasian) from California were randomly assigned to an intervention (access to a tailored website and weekly emails) or wait-list control group. Participants completed web-based assessments of physical activity, stage of behavior change, and psychosocial variables at baseline, one month, two months, and three months. Data were collected during 2006-2007. Multilevel random coefficient modeling examined group differences in rates of change. As compared to the control condition, the intervention group increased walking (+69 versus +32 min per week) and total moderate-to-vigorous physical activity (+23 versus -25 min per week) after three months. The intervention did not impact stage of behavior change or any of the other psychosocial variables. A tailored, Internet-based intervention for adult women had a positive effect on walking and moderate-to-vigorous physical activity in an ethnically-diverse sample. However, given the lack of comparable research contact in the control group, these findings should be taken cautiously. | 18,977,243 |
Does senescence give rise to disease? | The distinctions between senescence and disease are blurred in the literature of evolutionary biology, biodemography, biogerontology and medicine. Theories of senescence that have emerged over the past several decades are based on the concepts that organisms are a byproduct of imperfect structural designs built with imperfect materials and maintained by imperfect processes. Senescence is a complex mixture of processes rather than a monolithic process. Senescence and disease have overlapping biological consequences. Senescence gives rise to disease, but disease does not give rise to senescence. Current data indicate that treatment of disease can delay the age of death but there are no convincing data that these interventions alter senescence. An understanding of these basic tenets suggests that there are biological limits to duration of life and the life expectancy of populations and reveal biological domains where the development of interventions and/or treatments may modulate senescence. | 18,977,242 |
Assessing time-dependent association between scalp EEG and muscle activation: A functional random-effects model approach. | This study investigates time-dependent associations between source strength estimated from high-density scalp electroencephalogram (EEG) and force of voluntary handgrip contraction at different intensity levels. We first estimate source strength from raw EEG signals collected during voluntary muscle contractions at different levels and then propose a functional random-effects model approach in which both functional fixed effects and functional random-effects are considered for the data. Two estimation procedures for the functional model are discussed. The first estimation procedure is a two-step method which involves no iterations. It can flexibly use different smoothing methods and smoothing parameters. The second estimation procedure benefits from the connection between linear mixed models and regression splines and can be fitted using existing software. Functional ANOVA is then suggested to assess the experimental effects from the functional point of view. The statistical analysis shows that the time-dependent source strength function exhibits a nonlinear feature, where a bump is detected around the force onset time. However, there is the lack of significant variations in source strength on different force levels and different cortical areas. The proposed functional random-effects model procedure can be applied to other types of functional data in neuroscience. | 18,977,246 |
Is GPR39 the natural receptor of obestatin? | GPR39, an orphan receptor belonging to the family of G protein-coupled receptors, was originally reported to be the receptor of obestatin. However recently, numerous reports have questioned this conclusion. In mammals, GPR39 was reported to be involved in the regulation of gastrointestinal and the metabolic functions. In this article, a latest and brief review on the receptor family, structure, distribution and physiological functions of GPR39 has been reported. | 18,977,259 |
Exploring transcriptional conservation between Ancylostoma caninum and Haemonchus contortus by oligonucleotide microarray and bioinformatic analyses. | In this study, we identified, using an established oligonucleotide microarray platform for the parasitic nematode Haemonchus contortus, transcripts that are 'conserved' between serum-activated and non-activated L3s of Ancylostoma caninum (aL3 and L3, respectively) and H. contortus by cross-species hybridization (CSH) at high stringency and conducted extensive bioinformatic analyses of the cross-hybridizing expressed sequence tags (ESTs). The microarray analysis revealed significant differential hybridization between aL3 and L3 for 32 molecules from A. caninum, of which 29 were shown to have homologues/orthologues in the free-living nematode Caenorhabditis elegans and/or A. caninum and the other three molecules had no homologues in current gene databases. 'Non-wildtype' RNAi phenotypes were recorded for 13 of the C. elegans homologues. A subset of 16 C. elegans homologues/orthologues (i.e. genes abce-1, act-2, C08H9.2, C55F2.1, calu-1, col-181, cpr-6, elo-2, asp-1, K07E3.4, rpn-2, sel-9, T28C12.4, hsb-1, Y57G11C.15 and ZK593.1) were predicted to interact genetically with a total of 156 (range 1-88) other genes. Gene ontology (GO) analysis of the interacting genes revealed that the most common subcategories were signal transduction (7%), intracellular protein transport and glycolysis (6.2%) within 'biological process'; nuclear (25.7%) and intracellular (19.8%) within 'cellular component'; and ATP-binding (14.4%) and protein-binding (8.4%) within 'molecular function'. The potential roles of key molecules in the two blood-feeding parasitic nematodes are discussed in relation to the known roles of their homologues/orthologues in C. elegans. The CSH approach used may provide a tool for the screening of genes conserved across a range of different taxa of parasites for which DNA microarray platforms are not available. | 18,977,290 |
Labyrinthulomycetes phylogeny and its implications for the evolutionary loss of chloroplasts and gain of ectoplasmic gliding. | The labyrinthulomycetes, also known as the 'Labyrinthulomycota' are saprotrophic or less frequently parasitic stramenopilan protists, usually in marine ecosystems. Their distinguishing feature is an 'ectoplasmic net,' an external cytoplasmic network secreted by a specialized organelle that attaches the cell to its substrate and secretes digestive enzymes for absorptive nutrition. In this study, one of our aims was to infer the phylogenetic position of the labyrinthulomycetes relative to the non-photosynthetic bicoeceans and oomycetes and the photosynthetic ochrophytes and thereby evaluate patterns of change from photosynthesis to saprotrophism among the stramenopiles. For the labyrinthulomycetes, we determined sequences of the actin, beta-tubulin, and elongation factor 1-alpha gene fragments and where necessary, ribosomal small subunit (SSU) genes. Multilocus analysis using standard tree construction techniques not only strongly supported the oomycetes as the sister group to the phototrophic stramenopiles, but also, for the first time with moderate statistical support, showed that the labyrinthulomycetes and the bicoecean as sister groups. The paraphyly of the non-photosynthetic groups was consistent with independent loss of photosynthesis in labyrinthulomycetes and oomycetes. We also wished to develop a phylogenetically based hypothesis for the origin of the gliding cell bodies and the ectoplasmic net found in some labyrinthulomycetes. The cells of species in Labyrinthula and Aplanochytrium share a specialized form of motility involving gliding on ectoplasmic tracks. Before our study, only ribosomal DNA genes had been determined for these genera and their phylogenetic position in the labyrinthulomycetes was equivocal. Multilocus phylogenies applying our newly determined protein-coding sequences divided the labyrinthulomycetes between sister clades 'A' and 'B' and showed that the monophyletic group containing all of the gliding species was nested among non-gliding species in clade B. This phylogeny suggested that species that glide via an ectoplasm evolved from species that had used the ectoplasm mainly for anchorage and assimilation rather than motility. | 18,977,305 |
Do informed consent documents matter? | This commentary argues that, despite extensive critiques of informed consent documents, there are several ethical and legal reasons for investigators and IRB members to take these documents seriously. | 18,977,313 |
Regulating the conversion between rounded and elongated modes of cancer cell movement. | Switching between elongated and rounded modes of movement allows invasive tumor cells to adapt to varying microenvironments. In a recent issue of Cell, Sanz-Moreno et al. identify DOCK3, NEDD9, WAVE2, and ARHGAP22 as key molecules regulating Rac and Rho signaling that determine the mode of movement driving melanoma cell metastasis. | 18,977,323 |
miR-296 regulates growth factor receptor overexpression in angiogenic endothelial cells. | A key step in angiogenesis is the upregulation of growth factor receptors on endothelial cells. Here, we demonstrate that a small regulatory microRNA, miR-296, has a major role in this process. Glioma cells and angiogenic growth factors elevate the level of miR-296 in primary human brain microvascular endothelial cells in culture. The miR-296 level is also elevated in primary tumor endothelial cells isolated from human brain tumors compared to normal brain endothelial cells. Growth factor-induced miR-296 contributes significantly to angiogenesis by directly targeting the hepatocyte growth factor-regulated tyrosine kinase substrate (HGS) mRNA, leading to decreased levels of HGS and thereby reducing HGS-mediated degradation of the growth factor receptors VEGFR2 and PDGFRbeta. Furthermore, inhibition of miR-296 with antagomirs reduces angiogenesis in tumor xenografts in vivo. | 18,977,327 |
Identification of novel mutations in five patients with mitochondrial encephalomyopathy. | MELAS, MERRF, LHON and NARP, are well-established mitochondrial syndromes associated with specific point mutations of mitochondrial DNA (mtDNA). However, these recurrent mtDNA mutations account for only a minority of mitochondrial disease cases. To evaluate the impact of novel mtDNA mutations, we performed mtDNA sequence analysis in muscle and other tissues of 240 patients with different mitochondrial neuromuscular syndromes. We identified a total of 33 subjects with novel, private or uncommon mutations. Among these, five novel mutations were found in both paediatric and adult cases. We here report on the clinical description of these patients, as well as the biochemical and molecular genetic characterization of the corresponding mutations. Patients 1 and 2 showed changes in ND genes, patient 3 carried a heteroplasmic deletion in the COI gene, patients 4 and 5 carried heteroplasmic mutations in tRNA(Trp) and tRNA(Phe), respectively. Altogether, these data indicate that mtDNA analysis must become part of the routine screening for mitochondrial disorders. | 18,977,334 |
Suprachiasmatic nucleus slices induce molecular oscillations in fibroblasts. | The mammalian circadian pacemaker has been localized to the hypothalamic suprachiasmatic nucleus (SCN), where a set of clock genes and their resulting proteins form interlocking transcriptional/translational feedback loops to sustain molecular and functional oscillations. Interestingly, peripheral tissues and stimulated fibroblasts have also displayed daily oscillations, which are thought to be synchronized by the SCN in vivo. However, intercellular communications between the SCN and other tissues or cells remain poorly understood. Therefore, a novel co-culture model was established in the present study to understand the interactions between central and peripheral oscillators in co-cultures of SCN slices and NIH/3T3 cells in a serum-free condition. Expression profiles of Per1 and Rev-Erb alpha were measured in NIH/3T3 cells using real-time PCR. Results demonstrated that diffusible signals released from SCN slices could regulate molecular rhythms in cultured fibroblasts. Moreover, Rev-Erb alpha oscillation was more robust and appeared earlier than Per1. | 18,977,335 |
Visual evoked spread spectrum analysis (VESPA) responses to stimuli biased towards magnocellular and parvocellular pathways. | Stimulus contrast fluctuations were controlled while the properties of a novel ERP known as the VESPA (Visual Evoked Spread Spectrum Analysis) were examined using data from 8 healthy human subjects. Substantial differences were seen between the morphologies of VESPAs obtained using low contrast stimuli when compared with those obtained using high contrast and full contrast range stimuli. Topographic distributions for both responses are compared and the findings are considered in terms of the response characteristics of the magnocellular and parvocellular visual pathways and the VESPA method itself. | 18,977,382 |
Minocycline and neurodegenerative diseases. | Minocycline is a semi-synthetic, second-generation tetracycline analog which is effectively crossing the blood-brain barrier, effective against gram-positive and -negative infections. In addition to its own antimicrobacterial properties, minocycline has been reported to exert neuroprotective effects over various experimental models such as cerebral ischemia, traumatic brain injury, amyotrophic lateral sclerosis, Parkinson's disease, kainic acid treatment, Huntington' disease and multiple sclerosis. Minocycline has been focused as a neuroprotective agent over neurodegenerative disease since it has been first reported that minocycline has neuroprotective effects in animal models of ischemic injury [Yrjanheikki J, Keinanen R, Pellikka M, Hokfelt T, Koisinaho J. Tetracyclines inhibit microglial activation and are neuroprotective in global brain ischemia. Proc Natl Acad Sci USA 1998;95:15769-74; Yrjanheikki J, Tikka T, Keinanen R, Goldsteins G, Chan PH, Koistinaho J. A tetracycline derivative, minocycline, reduces inflammation and protects against focal cerebral ischemia with a wide therapeutic window. Proc Natl Acad Sci USA 1999;96:13496-500]. Recently, the effect of minocycline on Alzheimer's disease has been also reported. Although its precise primary target is not clear, the action mechanisms of minocycline for neuroprotection reported so far are; via; the inhibition of mitochondrial permeability-transition mediated cytochrome c release from mitochondria, the inhibition of caspase-1 and -3 expressions, and the suppression of microglial activation, involvement in some signaling pathways, metalloprotease activity inhibition. Because of the high tolerance and the excellent penetration into the brain, minocycline has been clinically tried for some neurodegenerative diseases such as stroke, multiple sclerosis, spinal cord injury, amyotropic lateral sclerosis, Hungtington's disease and Parkinson's disease. This review will briefly summarize the effects and action mechanisms of minocycline on neurodegenerative diseases. | 18,977,395 |
A new polysaccharide from leaf of Ginkgo biloba L. | A water-soluble polysaccharide, GPB, was obtained from leaf of Ginkgo biloba L by hot water extraction followed by precipitation with ethanol and fractionation with gel chromatography. The results of HPLC with TSK-GEL column and gel filtration chromatography with Sepharose CL-6B analysis indicated GPB was uniform in polarity and its molecular weight (MW) was about 10 kDa. The structure of GPB was analysed using chemical methods, IR spectroscopy, and NMR spectroscopy. GPB has a high branched structure with polygalactose as core part of backbone. The repeating unit of polygalactose consists of 1,6-linked Galactose (Gal) and 1,3,6-linked Gal. | 18,977,417 |
Feature-short and feature-long discrimination learning in the pigeon: conditional control of a two-event temporal map. | Eight pigeons were trained to peck an illuminated target key on discrete-trial fixed-interval schedules of reinforcement by food. Four birds were exposed to a feature-short (FS) task where a feature light signaled shortening of the forthcoming target-outcome interval from 30 to 15s, while the other four birds were exposed to a feature-long (FL) task where a feature light signaled extension of the forthcoming target-outcome interval from 15 to 30s. The discrimination performance measured by differential temporal distributions of pecks between featured and non-featured target trials suggested that the target-food temporal map was under conditional control of the feature light in both groups. The FS discrimination was more difficult to learn than the FL discrimination. This FS inferiority implies that our birds did not resort on the simple temporal discrimination by timing from the trial onset. The simple temporal discrimination account was also negated by the finding that increasing the feature-target gap did not have a predicted effect on the response distribution. | 18,977,418 |
Phylogenetic conservation of cytostatic factor related genes in the ascidian Ciona intestinalis. | In all vertebrates, mature oocytes arrest at the metaphase of the II meiotic division, while some invertebrates arrest at metaphase-I, others at prophase-I. Fertilization induces completion of meiosis and entry into the first mitotic division. Several experimental models have been considered from both vertebrates and invertebrates in order to shed light on the peculiar aspects of meiotic division, such as the regulation of the cytostatic factor (CSF) and the maturation promoting factor (MPF) in metaphase I or II. Recently, we proposed the oocytes of ascidian Ciona intestinalis as a new model to study the meiotic division. Here, taking advantage of the recent publication of the C. intestinalis genome, we presented a phylogenetic analysis of key molecular components of the CSF-related machinery. We showed that the Mos/MAP kinase pathway is perfectly conserved in ascidians. We demonstrated the presence of a CSF-like activity in metaphase-I arrested C. intestinalis oocytes able to block cell division in two-cell embryos. We further investigated the regulation of CSF by demonstrating that both CSF and MPF inactivation, at the exit of metaphase-I, are independent from protein synthesis, indicating the absence of short-lived factors that regulate metaphase stability, as in other invertebrate species. The results obtained suggest that meiotic regulation in C. intestinalis resembles that of vertebrates, such as Xenopus accordingly to the position of this organism in the evolutionary tree. | 18,977,421 |
Effects and mechanisms of total glucosides of paeony on synoviocytes activities in rat collagen-induced arthritis. | The aim of the study was to investigate the effects of TGP, an active compound extracted from the roots of Paeonia lactiflora Pall, on the activities of synoviocytes in rats with collagen-induced arthritis (CIA) and its possible mechanisms. CIA was induced in male Sprague-Dawley (SD) rats immunized with chicken type II collagen (CII) in Freund's complete adjuvant (FCA). Synoviocytes proliferation was determined by 3-(4, 5-2dimethylthiazal-2yl) 2, 5-diphenyltetrazoliumbromide (MTT) assay. Tumor necrosis factor alpha (TNF-alpha), interleukin-1 (IL-1), prostaglandin E(2) (PGE(2)) and cyclic adenosine monophosphate (cAMP) levels in synoviocytes were measured by radioimmunoassay (RIA). E-prostanoid (EP)(2) and EP(4) receptors were analyzed by Western blot analysis. The results showed that TGP significantly inhibited the proliferation of synoviocytes, decreased the production of IL-1, TNF-alpha and PGE(2) and elevated the levels of cAMP. Further study showed that TGP could up-regulate the expression of EP(2) and EP(4). These results indicated that TGP might exert its anti-inflammatory effects through inhibiting the production of pro-inflammatory mediators in synoviocytes of CIA rats, which might be associated with its ability to regulate cAMP-dependent EP(2)/EP(4)-mediated pathway. | 18,977,427 |
Aedes FADD: a novel death domain-containing protein required for antibacterial immunity in the yellow fever mosquito, Aedes aegypti. | Microbial infections in insects activate a series of immune responses that culminate in the production of antimicrobial peptides (AMPs). In Drosophila, two signaling pathways, govern the challenge-dependent expression of AMPs; the Toll and IMD pathways. While AMPs have been the subject of much research in mosquitoes, the regulation of the pathways required for AMP expression remains largely unknown. We report here the identification of Aedes FADD (AeFADD), a death domain protein in Aedes aegypti. AeFadd is expressed in all immune-competent tissues and all developmental stages examined. At the transcriptional level, AeFadd transcripts increased when challenged with Escherichia coli but not Micrococcus luteus. In both cases, we observed the induction of two AMP genes; cecropin and defensin. Loss of AeFadd function by dsRNA interference impaired the inducible expression of both AMPs, and rendered adult mosquitoes susceptible to both types of bacteria. Identifying molecules that regulate mosquito immunity may help elucidate the factors that contribute to the vectorial capacity and provide insights into general mechanisms that regulate innate immunity. | 18,977,438 |
Molecular analysis of the Aedes aegypti carboxypeptidase gene family. | To gain a better understanding of coordinate regulation of protease gene expression in the mosquito midgut, we undertook a comprehensive molecular study of digestive carboxypeptidases in Aedes aegypti. Through a combination of cDNA cloning using degenerate PCR primers, and database mining of the recently completed A. aegypti genome, we cloned and characterized 18 A. aegypti carboxypeptidase genes. Bioinformatic analysis revealed that 11 of these genes belong to the carboxypeptidase A family (AaCPA-I through AaCPA-XI), and seven to the carboxypeptidase B gene family (AaCPB-I through AaCPB-VII). Phylogenetic analysis of 32 mosquito carboxypeptidases from five different species indicated that most of the sequence divergence in the carboxypeptidase gene family occurred prior to the separation of Aedes and Anopheles mosquito lineages. Unlike the CPA genes that are scattered throughout the A. aegypti genome, six of seven CPB genes were found to be located within a single 120 kb genome contig, suggesting that they most likely arose from multiple gene duplication events. Quantitative expression analysis revealed that 11 of the A. aegypti carboxypeptidase genes were induced up to 40-fold in the midgut in response to blood meal feeding, with peak expression times ranging from 3 to 36 h post-feeding depending on the gene. | 18,977,440 |
Epstein-Barr virus evasion of CD8(+) and CD4(+) T cell immunity via concerted actions of multiple gene products. | Upon primary infection, EBV establishes a latent infection in B cells, characterized by maintenance of the viral genome in the absence of viral replication. The Epstein-Barr Nuclear Antigen 1 (EBNA1) plays a crucial role in maintenance of the viral DNA episome and is consistently expressed in all EBV-associated malignancies. Compared to other EBV latent gene products, EBNA1 is poorly recognized by CD8(+) T lymphocytes. Recent studies are discussed that shed new light on the mechanisms that underlie this unusual lack of CD8(+) T cell activation. Whereas the latent phase is characterized by the expression of a limited subset of viral gene products, the full repertoire of over 80 EBV lytic gene products is expressed during the replicative phase. Despite this abundance of potential T cell antigens, which indeed give rise to a strong response of CD4(+) and CD8(+) T lymphocytes, the virus can replicate successfully. Evidence is accumulating that this paradoxical situation is the result of actions of multiple viral gene products, inhibiting discrete stages of the MHC class I and class II antigen presentation pathways. Immediately after initiation of the lytic cycle, BNLF2a prevents peptide-loading of MHC class I molecules through inhibition of the Transporter associated with Antigen Processing, TAP. This will reduce presentation of viral antigens by the large ER-resident pool of MHC class I molecules. Synthesis of new MHC class I molecules is blocked by BGLF5. Viral-IL10 causes a reduction in mRNA levels of TAP1 and bli/LMP2, a subunit of the immunoproteasome. MHC class I molecules present at the cell surface are downregulated by BILF1. Also the antigen presenting capacity of MHC class II molecules is severely compromised by multiple EBV lytic gene products, including gp42/gH/gL, BGLF5, and vIL-10. In this review, we discuss how concerted actions of these EBV lytic proteins result in highly effective interference with CD8(+) and CD4(+) T cell surveillance, thereby providing the virus with a window for undisturbed generation of viral progeny. | 18,977,445 |
The role of electron transport in the defence response of the South African abalone, Haliotis midae. | In order to establish health management systems for farmed abalone, it is necessary to understand how the abalone immune system functions and responds to stimulation. Two electron transport system genes, cytochrome b and cytochrome c oxidase III, were found to be upregulated in a cDNA microarray experiment performed on haemocytes from immune-stimulated abalone (Arendze-Bailey, unpublished). The current study sought to elucidate the role of these genes, and thus the electron transport system, in the abalone immune response by specifically inhibiting cytochrome b with antimycin A and measuring haemocyte immune parameters in vivo. Antimycin A did not decrease haemocyte cell viability, but halved cellular ATP from 4 x 10(12) nM/cell to 2 x 10(12) nM/cell (p < 0.05, unpaired t-test). Inhibition of electron transport resulted in a 0.6 fold increase in cellular superoxide levels (p < 0.05, unpaired t-test), while phagocytosis dropped by nearly 50% (p < 0.05, ANOVA) and the ability of haemocytes to kill bacteria was also reduced. Since cytochrome b and cytochrome c oxidase III expression is upregulated in immune-stimulated abalone, and inhibition of electron transport resulted in a decreased immune response in vivo, we conclude that the abalone immune response is dependent on electron transport and that oxidative phosphorylation plays a role in the immune response following stimulation. | 18,977,446 |
The Val432Leu polymorphism of the CYP1B1 gene is associated with differences in estrogen metabolism and bone density. | Polymorphisms of the CYP450 genes that encode for the enzymes that metabolize estrogen are linked to hormone-related cancers. We investigated the impact of two polymorphisms of the CYP1B1 gene previously reported to be associated with hormone-related disorders on estrogen metabolism and bone mineral density (BMD), another hormone-dependent condition, in women from different ethnic backgrounds. Four hundred sixty-eight postmenopausal Caucasian women, 220 from St. Louis, MO, USA (mean age=63.5+/-0.53 years) and 248 from Palermo, Italy (mean age=72.9+/-0.44 years) participated in the study. Measurements of urinary estrogen metabolites by enzyme-linked immunoassay, serum estradiol by ultrasensitive radioimmnunoassay, and serum sex hormone-binding globulin by immunoradiometric assay were performed only in the American women, while BMD by dual energy X-ray absorptiometry and genotyping by pyrosequencing were performed in both American and Italian women. Differences in the levels of metabolites, free estradiol index and BMD were analyzed by analysis of covariance. Analysis among the American participants for the Valine432Leucine polymorphism showed that, compared to women with the Val/Val genotype, women with the Leu allele (Val/Leu and Leu/Leu) had significantly higher log-transformed values of total urinary estrogen metabolite (ng/mg-creatinine) levels (1.23+/-0.04, 1.35+/-0.02, and 1.34+/-0.03; p=0.03), and significantly lower BMD (gm/cm(2)) in the lumbar spine (1.009+/-0.02, 0.955+/-0.01 and 0.931+/-0.02; p=0.03) and the femoral neck (0.748+/-0.02, 0.717+/-0.01 and 0.693+/-001, p=0.03) for the Val/Val, Val/Leu and Leu/Leu genotypes respectively. There were no significant differences in the urinary metabolites and BMD in the different genotypes for the Alanine119Serine polymorphism among the American women. Meanwhile, a separate analysis among the Italian women revealed no significant differences in BMD among the different genotypes for the two polymorphisms investigated. In conclusion, women with the Leu allele for the CYP1B1 Val432polymorphism have increased estrogen catabolism, as indicated by higher urinary estrogen metabolites, compared to those with Val/Val genotype. This may lead to relative hypoestrogenism and lower BMD in the lumbar spine and femoral neck in these women. Our data suggest that through its effect on the rate of estrogen catabolism, the Val432Leu polymorphism of the CYP1B1 gene may represent as a possible genetic risk factor for osteoporosis in American women. | 18,977,467 |
Self-defining memories in complicated grief. | There is increasing attention to the mechanisms underpinning maladaptive responses to bereavement. This study indexed self-defining memories in bereaved individuals with and without complicated grief (CG). Participants with and without complicated grief (N=40) were asked to describe three self-defining memories. Results showed that CG participants provided more self-defining memories involving the deceased. Both groups were equally likely to report their loved one's death as a self-defining moment, however, the no-CG group showed more evidence of benefit finding in their memory narratives and experienced less negative emotion on recall. The findings suggest that CG is associated with distinctive patterns of autobiographical memory that are linked to self-identity. The pattern is consistent with self-memory system models of autobiographical remembering, and suggests that grieving individuals who experience ongoing yearning for their loved one view their self-identity as more closely linked to the deceased are more distressed by memories involving the loss. | 18,977,471 |
Formation and structure elucidation of N-(2,3,4-tri-O-acetyl-beta-D-glucopyranosyl)-N'-acetylthiourea. | Treatment with concd HCl/MeOH transformed N-(tetra-O-acetyl-beta-D-glucopyranosyl)-N'-acetylthiourea, via selective cleavage of the primary alcoholic ester group, into the title compound. | 18,977,474 |
Concentration determination of oxygen nanobubbles in electrolyzed water. | Water electrolysis is well known to produce solutions supersaturated with oxygen. The oxygen in electrolyzed solutions was analyzed with a dissolved oxygen meter and the Winkler method of chemical analysis. The concentration of oxygen measured with the dissolved oxygen meter agreed with that obtained using the Winkler method. However, measurements using a 10-fold dilution method showed a larger concentration of dissolved oxygen compared to the above methods. We developed a modified Winkler method to measure total oxygen concentration more accurately, which agreed with the results obtained from the 10-fold dilution experiment. The difference in measurements is due to the existence of oxygen nanobubbles, as confirmed by the observation of dynamic light scattering using a laser. Further analysis of the oxygen nanobubbles demonstrated that the stability of the nanobubbles was sufficient for chemical reaction and solvation to bulk solution. | 18,977,493 |
Experimental infection of an African dormouse (Graphiurus kelleni) with monkeypox virus. | Suitable animal models are needed to study monkeypox virus (MPXV) as human monkeypox clinically resembles smallpox and MPXV is a zoonotic and potential bioterroristic agent. We have demonstrated that a species of African dormice, Graphiurus kelleni, is susceptible to a lethal infection of MPXV and that MPXV replicated in multiple organs of this species. Following intranasal administration, MPXV replicated locally in the nasal mucosa causing necrosis and hemorrhage with subsequent systemic spread to lymph nodes, spleen, liver, and other tissues where it caused severe necrosis and/or hemorrhage leading to death. The dormouse model was validated for testing prophylactic (Dryvax vaccine) and therapeutic (cidofovir) test articles against intranasal challenges with MPXV. | 18,977,501 |
Leaching of brominated flame retardants from TV housing plastics in the presence of dissolved humic matter. | In this study, we investigated the contents of several brominated compounds in TV molding plastics, as well as their leaching characteristics in the presence of DHM. The PBDE content was about 3% of the sample weight, and deca-BDE was the most abundant homologue, accounting for over 80% of the total amount. TBBPA, PBPs and PBBs content was 8100, 4700 and 250 ng/g, respectively. Despite no detection of most of the lower brominated DEs in distilled water, most homologues could be detected in DHM solution, and their solubility increased according to the contact time; those of highly brominated compounds increased to 10 times their maximum solubility in distilled water. Especially, contrary to the relatively faster equilibrium in distilled water, BFR solubility in DHM solution was maintained even after 20 days. In addition, a modified first-order model adequately reflected rapid desorption for each compound in the initial period, but slow desorption afterwards. From an overall perspective, it is clear that hydrophobic BFRs can leach out to a great extent in the presence of DHM, which is a matter of great concern in E&E waste as the potential contaminant source of BFRs, especially in landfills and open dump sites that provide the perfect conditions for exposure of BFRs to abundant DHM. | 18,977,511 |
Shifting the bell curve: the benefits and costs of raising student achievement. | Benefit-cost analysis was conducted to estimate the increase in earnings, increased tax revenues, value of less crime, and reductions in welfare costs attributable to nationwide implementation of rapid assessment, a promising intervention for raising student achievement in math and reading. Results suggest that social benefits would exceed total social costs by a ratio of 28. Fiscal benefits to the federal government would exceed costs to the federal treasury by a ratio of 93. Social benefits would exceed costs to each state treasury by a ratio no lower than 286, and fiscal benefits would exceed costs to each state treasury by a ratio no lower than 5, for all but two state treasuries. Sensitivity analyses suggest that the findings are robust to a 5-fold change in the underlying parameters. | 18,977,534 |
Protein kinase C-beta inhibition for diabetic kidney disease. | Amid the rapidly rising number of people with diabetes worldwide, the prevalence of diabetic kidney disease (DKD) is expected to increase considerably despite available treatments. Consequently, novel therapeutic agents are urgently needed. Ruboxistaurin mesylate is a bisindolylmaleimide that specifically inhibits the beta isoform of protein kinase C (PKC). In experimental models of DKD, ruboxistaurin normalized glomerular hyperfiltration, decreased urinary albumin excretion, preserved kidney function, and reduced mesangial expansion, glomerulosclerosis, and tubulointerstitial fibrosis. These beneficial effects of ruboxistaurin, both alone and combined with renin-angiotensin system inhibition, have been observed in a variety of experimental models of DKD. A phase 2 study of PKC-beta inhibition in persons with type 2 diabetes and DKD already treated with angiotensin converting enzyme inhibition and/or angiotensin receptor blockade has been conducted. Addition of ruboxistaurin for 1 year reduced urinary albumin, prevented an increase in urinary transforming growth factor-beta, and stabilized estimated glomerular filtration rate. Based on secondary analyses of clinical trials in patients with diabetic retinopathy or neuropathy, ruboxistaurin appears safe and may also prevent onset of DKD. PKC-beta inhibition holds promise as a new strategy to improve kidney disease outcomes in diabetes. Large-scale clinical trials will be required to confirm safety and to validate prospective benefits of ruboxistaurin on relevant clinical endpoints in DKD. | 18,977,550 |
Ozone and urban forests in Italy. | Ozone levels along urban-to-rural gradients in three Italian cities (Milan, Florence, Bari) showed that average AOT40 values at rural and suburban sites were 2.6 times higher than those determined at urban sites. However, O(3) also exceeded the European criteria to protect forest health at urban sites, even when the standards for human health protection were met. For protecting street trees in Mediterranean cities, the objectives of measurement at urban sites should extend from the protection of human health to the protection of vegetation as well. A review of forest effects on O(3) pollution and of O(3) pollution on forest conditions in Italian cities showed that it was not possible to distinguish the effect of O(3) in the complex mixture of urban pollutants and stressors. A preliminary list of tree species for urban planning in the Mediterranean area shows the average tree capacity of O(3) removal and VOC emission. | 18,977,568 |
Background ozone in the southern Europe and Mediterranean area: influence of the transport processes. | The troposphere is subject to continuous inputs, production and removal processes of ozone and its precursors from natural processes and human activities acting together within a very complex system. In order to assess the behaviour of background ozone in the Mediterranean area, a description of trends, seasonal and diurnal behaviours of free tropospheric ozone is provided. In the Mediterranean area and southern Europe the background tropospheric ozone concentration appears significantly affected by three main air mass transport processes: (i) transport of polluted air masses on regional and long-range scales, (ii) downward transport of stratospheric air masses, and (iii) transport of mineral dust from the Sahara desert. In this review of the literature of the last two decades, we present an overview of these phenomena, mainly monitored at high baseline mountain stations representative of background atmospheric conditions. | 18,977,575 |
Who is hurt by procyclical mortality? | There is renewed interest in understanding how fluctuations in mortality and in health are related to fluctuations in economic conditions. The traditional perspective that economic recessions lower health and raise mortality has been challenged by recent findings that reveal mortality is actually procyclical. The epidemiology of the phenomenon - traffic accidents, cardiovascular disease, and smoking and drinking - suggests that socioeconomically vulnerable populations might be disproportionately at risk of "working themselves to death" during periods of heightened economic activity. In this paper, I examine mortality by individual characteristic during the 1980s and 1990s using the U.S. National Longitudinal Mortality Study. I find scant evidence that disadvantaged groups are significantly more exposed to procyclical mortality. Rather, working-age men with more education appear to bear a heavier burden, while those with little education experience countercyclical mortality. | 18,977,577 |
Complications of anterior surgery in cervical spine trauma: an overview. | Although anterior surgery for cervical spine injuries is a widespread procedure, articles regarding its overall complications are infrequently published in the literature. In the current study we focus on the complications encountered after anterior instrumented stabilization of cervical spine injuries and we discuss ways to minimize them. Patients with unstable lower cervical spine injuries who underwent anterior surgery over a 15-year period were identified and 74 patients with adequate follow-up were included in the study. Indication for surgery was set by the instability criteria of White and Panjabi. Demographic information, initial neurological examination, surgical reports, imaging findings and follow-up records were evaluated. Complications were classified as intraoperative (technique-related) and postoperative. Although radiological "complications" were noted, they had no or minor clinical consequences for the patient. We identified 9 patients with clinically significant complications: no purchase of the screws, late angulation deformity, screw breakage, backout of the screws and postoperative hematoma. Overall, 3 out of 74 patients (4%) were reoperated due to significant screw backout causing dysphagia, no purchase of the screws being completely in the adjacent disc and screw breakage, respectively. Anterior surgery for cervical spine injuries can present several complications, yet the technique is in a way permissive, even during the learning curve. Considering the significant morbidity of these patients, the reported rate of clinically significant complications is considered acceptable, and it could be further minimized by good preoperative planning, careful surgical technique and the use of modern implants and instrumentation. | 18,977,582 |
Blood flow velocity in the arteries of the anterior cerebral artery complex in patients with an azygos anterior cerebral artery aneurysm: a transcranial color-coded sonography study. | It is presumed that increased blood flow through the single azygos anterior cerebral artery (Az) may contribute to the formation of an Az aneurysm. The aim of this study was to assess the blood flow velocities in the arteries of the anterior cerebral artery (ACA) complex in patients with the Az aneurysm. A series of three patients (2 men, aged: 65, 52 and 41) with an aneurysm (unruptured in two cases) of the distal Az was examined. Blood flow velocities in the Az and the A1 segment of the ACA were measured by means of a transcranial color-coded duplex sonography (TCCS) and the Az to A1 segment (Az/A1) velocity ratio was calculated. The control group consisted of 22 healthy subjects (mean age: 44 years). There was a trend toward decreased (p=0.06) mean blood flow velocity in the Az compared to the A2 segment of the ACA of the control group. Blood velocity in the A1 segment did not differ between the study and control groups. Pulsatility and resistance indices in the Az were similar to those in the A2 segment of the control group. There were no differences between the Az/A1 ratio in the study group and the A2/A1 velocity ratio in the control group. Our results suggest that Az aneurysms are not associated with increased blood flow velocity in the Az. Possibly, a hemodynamic stress related to the Az bifurcation geometry, together with a bent course of this artery around the genu of the corpus callosum, predispose to aneurysm formation. | 18,977,588 |
Suppression of androgen receptor signaling and prostate specific antigen expression by (-)-epigallocatechin-3-gallate in different progression stages of LNCaP prostate cancer cells. | The green tea polyphenol, (-)-epigallocatechin-3-gallate (EGCG), inhibits the development and progression of prostate cancer in TRAMP mice and in men. We examined the effects of EGCG on LNCaP human prostate cancer sublines 104-S, 104-R1 and R1Ad representing different progression stages of prostate cancer. EGCG suppressed cell proliferation, prostate specific antigen (PSA) expression, and AR transcriptional activity in the different LNCaP sublines. Intraperitoneal administration of EGCG also suppressed the growth of relapsing R1Ad tumors and decreased tumor-derived serum PSA. Effects of EGCG on tumor PSA expression have the potential to affect accurate monitoring of patient tumor burden by serum PSA measurements. | 18,977,589 |
Hydrogeochemistry and arsenic contamination of groundwater in the Ganges Delta Plain, Bangladesh. | Geochemical composition and the level of Arsenic (As) contamination of groundwater in the Ganges Delta Plain, southwestern Bangladesh were elucidated. Hydrogeochemical data of tube well samples suggested that the groundwater is mostly Ca-Mg-HCO(3) type with bicarbonate (HCO(3)(-)) as the dominant anion, though other type waters are also observed. In contrast, the elevated EC, Cl(-) and high content of Na(+) relative to Ca(2+), Mg(2+) and K(+) in six groundwater samples suggest their saline origin. Low concentrations of NO(3)(-) and SO(4)(2-), and high concentrations of dissolved organic carbon (DOC), HCO(3)(-) and PO(4)(3-) indicate the reducing conditions of subsurface aquifer where sediments are deposited with abundant organic matter. The total As concentration in the analyzed samples is very high (0.0431-1.352 mg/L) along with high Fe (2.791-17.058 mg/L) and relatively low Mn (0.134-1.972 mg/L) at different depths. Distinct relationship of As with Fe and Mn, and strong correlation with DOC suggests that the biodegradation of organic matter and reductive dissolution of Fe-oxyhydroxide is considered to be the dominant processes to release As in aquifers. Moreover, negative correlation between As and SO(4)(2-) demonstrates the As may not be directly mobilized from sulfide minerals like arsenopyrite. | 18,977,593 |
Studies on Neospora caninum DNA detection in the oocytes and embryos collected from infected cows. | Neosporosis is a major cause of abortion in cattle over the world. One of the methods of preventing vertical transmission within the herd is to avoid breeding replacement heifers from infected dams. Another procedure suggested and recommended by the International Embryo Transfer Society (IETS) is embryo transfer (ET) from infected dams into uninfected recipients. Oocytes and embryos taken from seropositive cows were examined for the presence of Neospora caninum DNA. A modified PCR protocol using Np21 and Np6 primers was applied to detect parasite DNA in the samples. The expected 328 bp product was not obtained in oocytes and/or embryos collected from seropositive dams. The results confirmed that transfer of the embryos from seropositive donors into seronegative recipients is an appropriate method to eliminate vertical transmission of neosporosis in a herd. The present study demonstrated that oocytes and embryos are not exposed to N. caninum in the uterine cavity of seropositive dams. | 18,977,601 |
Periparturient use of parenteral micronised procaine penicillin to reduce the risk of clinical mastitis in heifers after calving. | Mastitis in primiparous heifers immediately postpartum can be both a significant welfare concern and a heavy economic loss. Interventions successfully researched include intramammary therapies. This study considered the clinical and practical effects of a parenteral approach to controlling clinical mastitis in heifers immediately postpartum. The objective of this field trial was to determine whether preventative treatment of heifers with a single parenteral treatment of 15 million iu micronised procaine penicillin within 12h after calving would reduce the incidence of clinical mastitis in early lactation as detected by farmers. All heifers (n=609) calving on three commercial dairy farms in New Zealand during the spring of 2006 were randomly allocated to either treatment or no treatment. Treatment (15 million iu micronised procaine penicillin) was given at the first milking following calving. All clinical mastitis was recorded. Treatment reduced the odds of having clinical mastitis within the first 7 days in milk by over half (Mantel-Haenszel adjusted OR=0.456; p=0.044); and reduced the odds of having mastitis within the first 100 days in milk by just under half (Mantel-Haenszel adjusted OR=0.518; p=0.027). Treatment had a significant effect on increasing the median days to clinical mastitis (p=0.019; beta=1.961, LCI 1.117, UCI 3.445). Preventative treatment of heifers immediately following calving with 15 million iu micronised procaine penicillin parenterally could be of benefit as part of a control programme aimed at reducing the incidence of clinical mastitis in heifers in their first lactation. | 18,977,612 |
Reversal sign on ante- and postmortem brain imaging in a newborn: report of one case. | A 16-day-old female newborn was admitted to the emergency department after cardiopulmonary arrest. Total-body radiographs and non-enhanced CT of the brain showed fracture of the right clavicle, pericerebral hemorrhage and brain damage with reversal sign. The infant died on the day of her hospital admission. Because child abuse was suspected, a medicolegal autopsy was ordered by the legal authorities. Prior to autopsy, total-body MRI and CT were performed. Results of the ante- and postmortem investigations were compared with each other and then with the autopsy findings. Postmortem brain imaging showed persistence of the reversal sign. To the best of our knowledge, this is the first case describing hypoxic ischemic damage of the brain parenchyma on antemortem CT and persisting on postmortem imaging in a child abuse case. | 18,977,623 |
[Depression and pain: prevalence and clinical implication]. | Somatic pains are frequent in patients with major depression. Although they are not included in classical symptoms of depression, physical pains are found in 50-90% of depressed patient. They are more frequent in severe depressions, and especially in psychiatric inpatients with depression. Physical painful symptoms are good indices of depression severity and namely are predictive of poorer responses to treatments, and then of elevated rates of relapse when pains are persistent as residual symptoms after remission of the episode. More frequent pains in depressive patients are headaches, limb, back and joint pains. Aetiological hypothesis to explain the coexistence of physical pains and depression are based on the well-known dysfunction of the serotonergic and noradrenergic pathways in depression, which explains mood symptoms but also a lack of inhibitory control of ascending pain messages, normally controlled in spinal cord by descending serotonergic and noradrenergic projections. This phenomenon could explain the development of an interoceptive painful hypersensitivity, without external sensitivity. Antidepressants with dual serotonergic and noradrenergic actions are efficacious to treat chronic pains, for example in diabetic neuropathy. In line with monoaminergic hypotheses shown above, this is in favour of the use of these serotonin and norepinephrine reuptake inhibitors in depression with important physical pains, but this issue needs further confirmation studies. | 18,977,630 |
Primary total hip arthroplasty in severe developmental dysplasia of the hip. Ten-year results using a cementless modular stem. | We report the average 10-year clinical and radiographic results of 28 hips with Crowe III or IV developmental dysplasia of the hip (DDH) and a technically difficult primary hip arthroplasty using the cementless modular S-ROM stem (DePuy Orthopedics, Warsaw, Ind). Twenty-one patients required significant autologous bone grafting, 1 had a large allograft, and 6 patients required femoral shortening at the time of their total hip arthroplasty. Three patients had an intraoperative technical complication. The average preoperative Harris hip score was 37; at 10 years, 81. The Short Form 12 was 41.64 physical/54.03 mental at 10 years, and the WOMAC average score was 23 at 10 years. None of the S-ROM stems had been revised or were loose at latest follow-up. Six hips had osteolysis in Gruen zones 1 or 7 but none around or distal to the sleeve. The 10-year results of the S-ROM stem used in patients with osteoarthritis secondary to severe DDH are excellent. | 18,977,633 |
Long-term remodeling in proximal femur around a hydroxyapatite-coated anatomic stem: ten years densitometric follow-up. | Bone remodeling after a hip arthroplasty has been quantified with dual energy x-ray absorptiometry, usually for short-term follow-up. We used this technique to determine the long-term remodeling produced by a hydroxyapatite-coated, anatomic stem. Eighty patients with unilateral hip osteoarthritis were included in the study. The contralateral, healthy hip was taken as control. Bilateral dual energy x-ray absorptiometry scans were done before the surgery, at 15 days, and 1 and 10 years postoperatively. There was a decrease of bone mineral density in zones 1 and 7, which ranged from 12.2% to 27.3% at the end of the first year. There were no changes in zones 1 to 6 from the 1st to the 10th year, but there was a late decrease, up to 42.9%, in zone 7. The changes of bone mineral density promoted by this stem occurred in the first postoperative year. Late loss was seen only in area 7. | 18,977,634 |
[Chronic daily headache in children and adolescents]. | Chronic daily headache (CDH) affects 2-4% of adolescent females and 0.8-2% of adolescent males. Chronic daily headache is diagnosed when headaches occur more than 4h/day, 15 headache days per month or more, over a period of 3 consecutive months, without an underlying pathology. It is manifested by severe intermittent, migraine-like headaches as well as by chronic baseline headaches. Both Silberstein-Lipton criteria and the second edition of the International Classification of Headache Disorders (ICHD) can be used to classify chronic daily headache in children and adolescents. Chronic daily headache is classified into four diagnostic categories: transformed (Silberstein-Lipton criteria)/chronic (ICHD) migraine, chronic tension-type headache, new daily persistent headache, and hemicrania continua. Children and adolescents with chronic daily headache frequently have sleep disturbance, pain at other sites, dizziness, medication-overuse headache, and a psychiatric comorbidity (anxiety and mood disorders). Chronic daily headache frequently results in school absence. Successful approaches to treatment include reassurance, education, use of preventative medication, avoidance of analgesics, and helping the child return to a functional daily routine and a regular school schedule. | 18,977,644 |
Fabrication of a highly sensitive penicillin sensor based on charge transfer techniques. | A highly sensitive penicillin biosensor based on a charge-transfer technique (CTTPS) has been fabricated and demonstrated in this paper. CTTPS comprised a charge accumulation technique for penicilloic acid and H(+) ions perception system. With the proposed CTTPS, it is possible to amplify the sensing signals without external amplifier by using the charge accumulation cycles. The fabricated CTTPS exhibits excellent performance for penicillin detection and exhibit a high-sensitivity (47.852 mV/mM), high signal-to-noise ratio (SNR), large span (1445 mV), wide linear range (0-25 mM), fast response time (<3s), and very good reproducibility. A very lower detection limit of about 0.01 mM was observed from the proposed sensor. Under optimum conditions, the proposed CTTPS outstripped the performance of the widely used ISFET penicillin sensor and exhibited almost eight times greater sensitivity as compared to ISFET (6.56 mV/mM). The sensor system is implemented for the measurement of the penicillin concentration in penicillin fermentation broth. | 18,977,651 |
Gene expression predictors in breast cancer: current status, limitations and perspectives. | Breast cancer is characterised by a wide heterogeneity regarding outcome and drug sensitivity. A better prediction of these two parameters at the individual level should improve patient management and therefore also improve both the quality of life and the overall survival of the patient. Several molecular predictors for prognosis (MammaPrint or Oncotype DX) and drug prediction (DLD30, SET index) have been generated using DNA-based arrays or RT-PCR, some of these being tested in phase III trials. Although they exhibit good metric performance and should improve the quality of care in the next decade, these predictors are considered suboptimal regarding the potential of the technology. New study design and arrays should generate more powerful second generation gene signatures. | 18,977,656 |
Synthesis, tubulin assembly, and antiproliferative activity against MCF7 and NCI/ADR-RES cancer cells of 10-O-acetyl-5'-hydroxybutitaxel. | A highly efficient kinetic resolution of racemic cis-4-(2-tert-butyldimethylsilyloxy-1,1-dimethyl)ethyl-3-tert-butyldimethylsilyloxy-azetidin-2-one with 7-O-triethylsilylbaccatin III was carried out to furnish 10-O-acetyl-5'-hydroxybutitaxel after removal of the silyl protecting groups. The compound was 50% as active as paclitaxel in a tubulin assembly assay and showed significantly decreased activity against MCF7 cell proliferation compared to paclitaxel. | 18,977,659 |
Irreversible inhibition of dihydrodipicolinate synthase by 4-oxo-heptenedioic acid analogues. | We report the synthesis of (2E,5E)-4-oxoheptadienedioic acid and (2E)-4-oxoheptenedioic acid and evaluation of both diester and diacid analogues as inhibitors of bacterial dihydrodipicolinate synthase. Enzyme kinetic studies allowed the determination of second-order rate constants of inactivation; and substrate co-incubation studies have shown the inhibitors act at the active-site. Mass spectrometric analyses have further explored the enzyme-inhibitor interaction and determined the sites of enzyme alkylation. | 18,977,662 |
Cholangiocarcinoma. | Cholangiocarcinoma is an uncommon adenocarcinoma with poor prognosis. Although the 1-year survival has increased over time, the 5-year survival has not shown any significant change (less than 5%). Cure can only be expected from surgical resection of early stage tumours but most patients initially present with advanced disease. Cancer cachexia, liver failure, and recurrent sepsis due to biliary obstruction are among the main causes of mortality. Patients' prognosis is strongly related to radical surgery and complete resection is the most effective therapy; the location within the biliary tree (proximal versus distal) has no impact on survival when a complete resection is achieved despite the fact the rate of resectability is up to 70% in case of distal cancer and 15-20% for high bile ducts tumours. Prognosis of cholangiocarcinoma remains poor even with aggressive surgical therapy because of the high incidence of local or regional recurrence and distant metastasis. Based on these data many questions need an answer: is there a role for adjuvant chemotherapy or radiotherapy? Neoadjuvant treatments provide best results? There is a standard therapy in unresectable or metastatic cholangiocarcinoma? This report tries to answer to frequently asked questions that the readers are faced with their patients every day (from diagnostic procedures to palliative treatment) and tries to suggest useful information for their professional practice. | 18,977,670 |
Surveillance of antibiotic resistance evolution and detection of class 1 and 2 integrons in human isolates of multi-resistant Salmonella Typhimurium obtained in Uruguay between 1976 and 2000. | To study the evolution of antibiotic resistance in isolates of Salmonella enterica subspecies enterica serovar Typhimurium (Salmonella Typhimurium) obtained in Uruguay between the years 1976 and 2000, and to determine the incidence of class 1 and 2 integrons in the multi-resistant isolates. We studied 258 strains of Salmonella Typhimurium from various sources, isolated between 1976 and 2000. We determined the evolution of antibiotic resistance and the distribution of class 1 and 2 integrons in all isolates by means of disk diffusion assays and PCR. During the period 1989-2000 resistance to streptomycin was 56.8%, tetracycline 13.6%, sulfonamides 11.2%, and ampicillin 7.2%. Resistance to gentamicin, kanamycin, chloramphenicol, and nalidixic acid were lower than 5%; no resistance was detected to fluoroquinolones, oxyiminocephalosporins, and amikacin. These results show a dramatic decrease with respect to values found in the period 1976-1988. In this period, resistance to streptomycin was 63.2%, tetracycline 36.8%, sulfonamides 32.3%, and ampicillin 27.8%. Throughout the two periods, 29 multi-resistant Salmonella Typhimurium strains were isolated harboring some class of integron: 15 strains had only intI2, 11 strains presented both intI1 and intI2, and three isolates only intI1. Our results show a marked decrease in resistance throughout these years, along with a correlation between resistance to different antibiotics and the presence of integrons. | 18,977,678 |
Spectrofluorimetric determination of fluoroquinolones in pharmaceutical preparations. | Simple, rapid and highly sensitive spectrofluorimetric method is presented for the determination of four fluoroquinolone (FQ) drugs, ciprofloxacin, enoxacin, norfloxacin and moxifloxacin in pharmaceutical preparations. Proposed method is based on the derivatization of FQ with 4-chloro-7-nitrobenzofurazan (NBD-Cl) in borate buffer of pH 9.0 to yield a yellow product. The optimum experimental conditions have been studied carefully. Beer's law is obeyed over the concentration range of 23.5-500 ng mL(-1) for ciprofloxacin, 28.5-700 ng mL(-1) for enoxacin, 29.5-800 ng mL(-1) for norfloxacin and 33.5-1000 ng mL(-1) for moxifloxacin using NBD-Cl reagent, respectively. The detection limits were found to be 7.0 ng mL(-1) for ciprofloxacin, 8.5 ng mL(-1) for enoxacin, 9.2 ng mL(-1) for norfloxacin and 9.98 ng mL(-1) for moxifloxacin, respectively. Intra-day and inter-day relative standard deviation and relative mean error values at three different concentrations were determined. The low relative standard deviation values indicate good precision and high recovery values indicate accuracy of the proposed methods. The method is highly sensitive and specific. The results obtained are in good agreement with those obtained by the official and reference method. The results presented in this report show that the applied spectrofluorimetric method is acceptable for the determination of the four FQ in the pharmaceutical preparations. Common excipients used as additives in pharmaceutical preparations do not interfere with the proposed method. | 18,977,686 |
Detection of viral RNA from paraffin-embedded tissues after prolonged formalin fixation. | Isolating amplifiable RNA from formalin-fixed, paraffin-embedded (FFPE) tissues is more difficult than isolating DNA because of RNases, chemical modification of the RNA, and cross-linking of nucleic acids and proteins. Tissues containing infectious disease agents that require biosafety level (BSL)-3 and -4 necessitate fixation times of 21 and 30 days, respectively. To improve procedures for extracting RNA from these FFPE tissues and detect the RNA with the more sensitive TaqManbased reverse transcriptase (RT)-PCR. Through a single modification of a commercially available kit, we were able to extract amplifiable RNA and detect West Nile virus (WNV), Marburg virus (MARV), and Ebola virus (EBOV)-infected tissues using TaqMan assays. Formalin fixation results in an approximately 2log(10) reduction in detection limit when compared to fresh tissues. Increasing proteinase K digestion (24h) improved extraction of amplifiable RNA from FFPE tissues. The TaqMan results were comparable to more traditional detection results such as virus isolation. This improved extraction procedure for obtaining RNA combined with the TaqMan RT-PCR assays permit retrospective and prospective studies on FFPE tissues infected with BSL-3 and -4 pathogens. | 18,977,691 |
Oligoclonal myelin-reactive T-cell infiltrates derived from multiple sclerosis lesions are enriched in Th17 cells. | In this study, acute and chronic brain and spinal cord lesions, and normal appearing white matter (NAWM), were resected post-mortem from a patient with aggressive relapsing-remitting multiple sclerosis (MS). T-cell infiltrates from the central nervous system (CNS) lesions and NAWM were separated and characterized in-vitro. All infiltrates showed a proliferative response against multiple myelin peptides. Studies of the T-cell receptor (TCR)Vbeta and Jbeta usage revealed a very skewed repertoire with shared complementarity-determining region (CDR)3 lengths detected in all CNS lesions and NAWM. In the acute lesion, genomic profiling of the infiltrating T-cells revealed up-regulated expression of TCRalpha and beta chain, retinoic acid-related orphan nuclear hormone receptor C (RORC) transcription factor, and multiple cytokine genes that mediate Th17 cell expansion. The differentially expressed genes involved in regulation of Th17 cells represent promising targets for new therapies of relapsing-remitting MS. | 18,977,698 |
Monitoring medication adherence by unannounced pill counts conducted by telephone: reliability and criterion-related validity. | Although demonstrated valid for monitoring medication adherence, unannounced pill counts conducted in patients' homes are costly and logistically challenging. Telephone-based unannounced pill counts offer a promising adaptation that resolves most of the limitations of home-based pill counting. We tested the reliability and criterion-related validity of a telephone-based unannounced pill count assessment of antiretroviral adherence. HIV-positive men and women (N = 89) in Atlanta, Georgia, completed a telephone-based unannounced pill count and provided contemporaneous blood specimens to obtain viral loads; 68 participants also received an immediate second pill count conducted during an unannounced home visit. A high degree of concordance was observed between the number of pills counted on the telephone and in the home (intraclass correlation [ICC] = .981, p < .001) and percent of pills taken (ICC = .987, p < .001). Adherence obtained by the telephone count and home count reached 92% agreement (Kappa coefficient = .94). Adherence determined by telephone-based pill counts also corresponded with patient viral load, providing evidence for criterion-related validity. Unannounced telephone-based pill counts offer a feasible objective method for monitoring medication adherence. | 18,977,718 |
Low rate of adverse hepatic events associated with fosamprenavir/ritonavir-based antiretroviral regimens. | To appraise the incidence of liver toxicity in a population of patients receiving fosamprenavir/ritonavir (FPV/r) with a high frequency of viral hepatitis co-infection. 636 patients, 341 (54%) with HCV antibodies and 38 (5.6%) bearing serum HBsAg, were recruited. All of them received FPV/r 700/100 twice every day. 93 (27%) patients who tested positive for HCV antibodies showed an AST to platelet ratio index (APRI) higher than 1.5, consistent with significant liver fibrosis. After a median (range) follow-up time of 6.91 (0.46-20.66) months, 3 (0.47%) patients developed grade 3 ALT elevation. All the former patients were hepatitis virus co-infected, 2 with hepatitis C virus and 1 with hepatitis B virus. The frequency of grade 3 ALT elevation in patients with HCV antibodies was 0.58% and in those harbouring HBsAg it was 2.63%. 4 (0.62%) patients suffered from a liver decompensation and 1 died due to a hepatic cause while on follow-up. No patients with APRI equal to or higher than 1.5 showed grade 3 ALT elevation. The incidence of adverse hepatic events in patients receiving FPV/r including combinations seems to be low, even in subjects co-infected with hepatitis virus and in those with significant liver fibrosis. | 18,977,719 |
Redox proteomics: basic principles and future perspectives for the detection of protein oxidation in plants. | The production and scavenging of chemically reactive species, such as ROS/RNS, are central to a broad range of biotic and abiotic stress and physiological responses in plants. Among the techniques developed for the identification of oxidative stress-induced modifications on proteins, the so-called 'redox proteome', proteomics appears to be the best-suited approach. Oxidative or nitrosative stress leaves different footprints in the cell in the form of different oxidatively modified components and, using the redox proteome, it will be possible to decipher the potential roles played by ROS/RNS-induced modifications in stressed cells. The purpose of this review is to present an overview of the latest research endeavours in the field of plant redox proteomics to identify the role of post-translational modifications of proteins in developmental cell stress. All the strategies set up to analyse the different oxidized/nitrosated amino acids, as well as the different reactivities of ROS and RNS for different amino acids are revised and discussed. A growing body of evidence indicates that ROS/RNS-induced protein modifications may be of physiological significance, and that in some cellular stresses they may act causatively and not arise as a secondary consequence of cell damage. Thus, although previously the oxidative modification of proteins was thought to represent a detrimental process in which the modified proteins were irreversibly inactivated, it is now clear that, in plants, oxidatively/nitrosatively modified proteins can be specific and reversible, playing a key role in normal cell physiology. In this sense, redox proteomics will have a central role in the definition of redox molecular mechanisms associated with cellular stresses. | 18,977,746 |
Photosynthetic properties of C4 plants growing in an African savanna/wetland mosaic. | Photosynthesis rates and photosynthesis-leaf nutrient relationships were analysed in nine tropical grass and sedge species growing in three different ecosystems: a rain-fed grassland, a seasonal floodplain, and a permanent swamp, located along a hydrological gradient in the Okavango Delta, Botswana. These investigations were conducted during the rainy season, at a time of the year when differences in growth conditions between the sites were relatively uniform. At the permanent swamp, the largest variations were found for area-based leaf nitrogen contents, from 20 mmol m(-2) to 140 mmol m(-2), nitrogen use efficiencies (NUE), from 0.2 mmol (C) mol(-1) (N) s(-1) to 2.0 mmol (C) mol(-1) (N) s(-1), and specific leaf areas (SLA), from 50 cm(2) g(-1) to 400 cm(2) g(-1). For the vegetation growing at the rain-fed grassland, the highest leaf gas exchange rates, high leaf nutrient levels, a low ratio of intercellular to ambient CO(2) concentration, and high carboxylation efficiency were found. Taken together, these observations indicate a very efficient growth strategy that is required for survival and reproduction during the relatively brief period of water availability. The overall lowest values of light-saturated photosynthesis (A(sat)) were observed at the seasonal floodplain; around 25 micromol m(-2) s(-1) and 30 micromol m(-2) s(-1). To place these observations into the broader context of functional leaf trait analysis, relationships of photosynthesis rates, specific leaf area, and foliar nutrient levels were plotted, in the same way as was done for previously published 'scaling relationships' that are based largely on C(3) plants, noting the differences in the analyses between this study and the previous study. The within- and across-species variation in both A(sat) and SLA appeared better predicted by foliar phosphorus content (dry mass or area basis) rather than by foliar nitrogen concentrations, possibly because the availability of phosphorus is even more critical than the availability of nitrogen in the studied relatively oligotrophic ecosystems. | 18,977,748 |
Extracellular ATP-induced NO production and its dependence on membrane Ca2+ flux in Salvia miltiorrhiza hairy roots. | Extracellular ATP (eATP) is a novel signalling agent, and nitric oxide (NO) is a well-established signal molecule with diverse functions in plant growth and development. This study characterizes NO production induced by exogenous ATP and examines its relationship with other important signalling agents, Ca(2+) and H(2)O(2) in Salvia miltiorrhiza hairy root culture. Exogenous ATP was applied at 10-500 microM to the hairy root cultures and stimulated NO production was detectable within 30 min. The NO level increased with ATP dose from 10-100 microM but decreased from 100-200 muM or higher. The ATP-induced NO production was mimicked by a non-hydrolysable ATP analogue ATPgammaS, but only weakly by ADP, AMP or adenosine. The ATP-induced NO production was blocked by Ca(2+) antagonists, but not affected by a protein kinase inhibitor. ATP also induced H(2)O(2) production, which was dependent on both Ca(2+) and protein kinases, and also on NO biosynthesis. On the other hand, ATP induced a rapid increase in the intracellular Ca(2+) level, which was dependent on NO but not H(2)O(2). The results suggest that NO is implicated in ATP-induced responses and signal transduction in plant cells, and ATP signalling is closely related to Ca(2+) and ROS signalling. | 18,977,749 |
Translation initiation factor 4B homodimerization, RNA binding, and interaction with Poly(A)-binding protein are enhanced by zinc. | The eukaryotic translation initiation factor (eIF) 4B promotes the RNA-dependent ATP hydrolysis activity and ATP-dependent RNA helicase activity of eIF4A and eIF4F during translation initiation. eIF4B also helps to organize the assembly of the translational machinery through its interactions with eIF4A, eIF4G, eIF3, the poly(A)-binding protein (PABP), and RNA. Although the function of eIF4B is conserved among plants, animals, and yeast, eIF4B is one of the least conserved of initiation factors at the sequence level. Mammalian eIF4B is a constitutive dimer; however, conflicting reports have suggested that plant eIF4B may exist as a monomer or a dimer. In this study, we show that eIF4B from wheat can form a dimer and we identify the region responsible for its dimerization. Zinc stimulated homodimerization of eIF4B and bound eIF4B with a Kd of 19.7 nM. Zinc increased the activity of the eIF4B C-terminal RNA-binding domain specifically. Zinc promoted the interaction between eIF4B and PABP but not the interaction between eIF4B and eIF4A or eIFiso4G, demonstrating that the effect of zinc was highly specific. The interaction between PABP and eIFiso4G was also stimulated by zinc but required significantly higher levels of zinc. Interestingly zinc abolished the ability of eIFiso4G to compete with eIF4B in binding to their overlapping binding sites in PABP by preferentially promoting the interaction between eIF4B and PABP. Our observations suggest that wheat eIF4B can dimerize but requires zinc. Moreover zinc controls the partner protein selection of PABP such that the interaction with eIF4B is preferred over eIFiso4G. | 18,977,752 |
Patients' preferences within randomised trials: systematic review and patient level meta-analysis. | To systematically review fully randomised patient preference trials and to explore the impact of preferences on attrition and outcome by meta-analysis of patient level data. Citation search using Science Citation Index and Google Scholar and search of the main electronic databases (Medline, CINAHL, Embase, and AMED) with a combination of key words. Fully randomised patient preference trials that compared treatments for any clinical condition were included. Other types of preference trials and crossover trials were excluded. Other inclusion criteria: participants aged 16 years and over; primary, self-reported outcomes measured on a continuous numerical scale. From 167 studies identified and screened, 17 were identified as fully randomised patient preference trials. Of the 17 trials identified, 11 authors provided raw data for the meta-analysis. Data collected were baseline and follow-up data for the main outcome, randomised allocation data, preference data, and demographic data. Baseline and first post-intervention follow-up data for the main outcome were standardised. To improve homogeneity, data for only the eight musculoskeletal trials (n=1594) were combined. To estimate the effects of preferences on outcomes and attrition, three groups were compared: patients who had a preference and were randomly allocated to their preferred treatment; patients who had a preference and were randomly allocated to the treatment they did not prefer; and patients who had no preference. Patients who were randomised to their preferred treatment had a standardised effect size greater than that of those who were indifferent to the treatment assignment (effect size 0.162, 95% confidence interval 0.011 to 0.314; P=0.04). Participants who received their preferred treatment also did better than participants who did not receive their preferred treatment (effect size 0.152, -0.035 to 0.339), although this was not statistically significant (P=0.11). Participants allocated to their undesired treatment had outcomes that were no different from those who were indifferent. Participants who were allocated to their undesired treatment were less likely to be lost to first follow-up compared with indifferent participants (odds ratio 1.70, 1.076 to 2.693; P=0.02). No difference was found in attrition between patients allocated to their preference and those who were indifferent. Preferences among patients in musculoskeletal trials are associated with treatment effects. In open randomised trials, preferences should be ascertained before randomisation. | 18,977,792 |
Radial artery anomaly and its influence on transradial coronary procedural outcome. | The transradial approach for percutaneous coronary procedures has the advantage of reduced access site complications but is associated with specific technical challenges in comparison with the transfemoral approach. Transradial procedure failures can sometimes be due to variation in radial artery anatomy. However, data describing such variations are limited. To evaluate the incidence and impact of radial artery anomalies in patients undergoing transradial coronary procedures. Retrograde radial arteriography was performed in all patients presenting for a first-time radial procedure. Patient characteristics, radial artery anatomy and procedural outcome were assessed. 1540 consecutive patients were studied, 70.6% male, mean (SD) age 63.6 (11.1) years. The overall incidence of radial artery anomaly was 13.8% (n = 212). 108 (7.0%) patients had a high-bifurcating radial origin, 35 (2.3%) had a full radial loop, 30 (2.0%) had extreme radial artery tortuosity and 39 (2.5%) had miscellaneous anomalies such as radial atherosclerosis and accessory branches. Overall transradial procedural success was 96.8%. Procedural failure was more common in patients with anomalous anatomy than in patients with normal anatomy (14.2% vs 0.9%, p<0.001). Procedural failure in patients with high radial bifurcation, radial loop, severe radial tortuosity and other anomalies was 4.6%, 37.1%, 23.3% and 12.9%, respectively. 15 (1%) vascular complications occurred, all of which were treated conservatively without ischaemic sequelae. Anomalous radial artery anatomy is relatively common and is a significant cause of procedural failure. Within each specific anomalous pattern there is a differential procedural failure rate. This has implications for clinical practice and suggests a need for imaging of the radial artery after sheath insertion. | 18,977,799 |
Folic acid use and major congenital malformations in offspring of women with epilepsy: a prospective study from the UK Epilepsy and Pregnancy Register. | In the general population, folic acid supplementation during pregnancy has been demonstrated to reduce the frequency of neural tube defects (NTDs) and other major congenital malformations (MCMs). It is recommended that women with epilepsy contemplating pregnancy take supplemental folic acid because of the known antifolate effect of some antiepileptic drugs (AEDs). Here the aim was to determine the effectiveness of this practice. This study is part of a prospective, observational, registration and follow-up study. Suitable cases are women with epilepsy who become pregnant and who are referred before outcome of the pregnancy is known. The main outcome measure is the MCM rate. Outcomes were analysed against folic acid exposure, malformation type and drug group for the most commonly used monotherapy AEDs. In 1935 cases reported to have received preconceptual folic acid, 76 MCMs (3.9%; 95% CI 3.1 to 4.9) and eight NTDs (0.4%; 95% CI 0.2 to 0.8) were identified. For 2375 women who were reported to have received folic acid but not until later in the pregnancy (n = 1825) or not at all (n = 550), there were 53 outcomes with an MCM (2.2%; 95% CI 1.7 to 2.9) and eight NTDs (0.34%; 95% CI 0.2 to 0.7). The study supports the view that extrapolation from studies carried out in the general population to groups of women with epilepsy may be questionable. It may be that the increased risk of MCM recorded in this group occurs through mechanisms other than that of folic acid metabolism. | 18,977,812 |
Voxel-based analysis of cerebral glucose metabolism in mono- and dizygotic twins discordant for Alzheimer disease. | Sporadic Alzheimer disease (AD) is a multifactorial disease to which both genetic and environmental factors contribute. Therefore, twin pairs are useful in studying its pathogenesis and aetiology. Cerebral glucose metabolism has been found to be reduced in AD patients. Cerebral glucose metabolism was studied in seven monozygotic (MZ) and nine same-sexed dizygotic (DZ) twin pairs discordant for AD using positron emission tomography. To obtain objective and explorative results concerning differences in glucose metabolism, the analysis was performed utilising modern voxel-based analysis methodology statistical parametric mapping and automated region-of-interest analysis. In the demented MZ and DZ co-twins, cerebral glucose metabolism was extensively reduced compared with controls. The non-demented MZ co-twins showed reduced metabolism in inferior frontal, lateral temporal, parietal and medial temporal cortices as well as in the thalamus, putamen and right amygdala. In contrast, no reductions were found in the non-demented DZ co-twins. The reduction found in the non-demented MZ co-twins may be an indicator of genetic susceptibility to AD. | 18,977,818 |
Neurological morbidity among human T-lymphotropic-virus-type-1-infected individuals in a rural West African population. | Community-based neurological data about human T lymphotropic virus type 1 (HTLV-1) morbidity in sub-Saharan Africa are scarce. To ascertain the prevalence of neurological morbidity, in particular tropical spastic paraparesis (TSP), among HTLV-1-infected subjects and to compare TSP prevalence in HTLV-1-infected with that in non-infected subjects in a rural West African population. A cross-sectional study of HTLV-1-infected cases and controls (ratio 4:1) from a rural community (population approximately 10 000, HTLV-1 prevalence 7.7%). One neurologist masked to HTLV-1 serological status assessed all subjects. Clinical criteria were employed to diagnose TSP. From 205 eligible cases and controls, 139 were recruited with a mean age of 56 years, and 113 (81%) were HTLV-1-infected. 108/139 (78%) were female, and 8/113 HTLV-1 infected cases (7.1%) had a definite or probable TSP (all females; mean age 67 years) compared with 0/26 controls. Two with TSP were co-infected with HIV-2. Complaints of back pain and leg weakness were more common in HTLV-1-infected individuals (p = 0.03, p = 0.02), but no single symptom distinguished between subjects with and without TSP. We report a prevalence of TSP among HTLV-1-infected persons in this rural West African setting of 7.1%. There are difficulties excluding other potential aetiologies here. | 18,977,823 |
Plasma vitamin B12 status and cerebral white-matter lesions. | Elevated homocysteine has been associated with a higher prevalence of cerebral white-matter lesions and infarcts, and worse cognitive performance. This raises the question whether factors involved in homocysteine metabolism, such as vitamin B(12), are also related to these outcomes. This study examined the association of several markers of vitamin B(12) status with cerebral white-matter lesions, infarcts and cognition. The study evaluated the association of plasma concentrations of vitamin B(12), methylmalonic acid, holotranscobalamin and transcobalamin saturation with cerebral white-matter lesions and infarcts at baseline and cognition at baseline and during follow-up among 1019 non-demented elderly participants of the population-based Rotterdam Scan Study. Analyses were adjusted for several potential confounders, including homocysteine and folate concentration. Poorer vitamin B(12) status was significantly associated with greater severity of white-matter lesions, in particular periventricular white-matter lesions, in a concentration-related manner. Adjustment for common vascular risk factors (including blood pressure, smoking, diabetes and intima media thickness) did not alter the associations. Adjustment for homocysteine and folate modestly weakened the associations. No association was observed for any of the studied markers of vitamin B(12) status with presence of brain infarcts and baseline cognition or cognitive decline during follow-up. These results indicate that vitamin B(12) status in the normal range is associated with severity of white-matter lesions, especially periventricular lesions. Given the absence of an association with cerebral infarcts, it is hypothesised that this association is explained by effects on myelin integrity in the brain rather than through vascular mechanisms. | 18,977,824 |
Hospital discharge of the high-risk neonate. | This policy statement updates the guidelines on discharge of the high-risk neonate first published by the American Academy of Pediatrics in 1998. As with the earlier document, this statement is based, insofar as possible, on published, scientifically derived information. This updated statement incorporates new knowledge about risks and medical care of the high-risk neonate, the timing of discharge, and planning for care after discharge. It also refers to other American Academy of Pediatrics publications that are relevant to these issues. This statement draws on the previous classification of high-risk infants into 4 categories: (1) the preterm infant; (2) the infant with special health care needs or dependence on technology; (3) the infant at risk because of family issues; and (4) the infant with anticipated early death. The issues of deciding when discharge is appropriate, defining the specific needs for follow-up care, and the process of detailed discharge planning are addressed as they apply in general to all 4 categories; in addition, special attention is directed to the particular issues presented by the 4 individual categories. Recommendations are given to aid in deciding when discharge is appropriate and to ensure that all necessary care will be available and well coordinated after discharge. The need for individualized planning and physician judgment is emphasized. | 18,977,994 |
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