title stringlengths 0 1.13k | abstract stringlengths 1 15.7k | PMID int64 22 36.5M |
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Investigations into conformational transitions and solvation structure of a 7-piperidino-5,9-methanobenzo[8] annulene in water. | Solvation shell structure of a 7-piperidino-5,9-methanobenzo[8] annulene (PMA) in water has been investigated in ambient conditions using both molecular dynamics (MD) and Car-Parrinello molecular dynamics (CPMD) calculations. From the MD calculations, we find that this molecule exists in three major conformational states out of which two are in twist-boat forms and one in chair form. Due to the limited time scale accessible in CPMD simulations, we have studied all the three conformational states separately using CPMD. The molecular geometry, electronic charge distribution and solvation structure for all three forms are investigated. The stability order of the chair and twist-boat conformations in water solvent has been reversed when compared to the gaseous phase results and in the case of polar aprotic solvents (J. Org. Chem., 1999, 61, 5979). From the radial distribution function, we find that the solvent density around the chair form is significantly lower, which has to be directly related to the smaller solvent accessible area for this conformation and this is in complete agreement with earlier reports. Among the findings are that the solvation shell structure around the nitrogen atom in the chair form of PMA is considerably different from the open conformational forms or the twist-boat forms. The dipole moment for the closed form is found to be significantly larger when compared to the twist-boat forms. | 18,846,303 |
Comparison between a GnRH agonist and a GnRH antagonist protocol for the same patient undergoing IVF. | In order to compare GnRH agonist with antagonist protocol for the same patient during controlled ovarian stimulation cycles, the in vitro fertilization and embryo transfer (IVF-ET) outcome was retrospectively studied in 81 patients undergoing 105 agonist protocols and 88 antagonist protocols. The results showed that there was no statistically significant difference in duration of ovarian stimulation, number of ampoules, oocytes retrieved, serum estradiol (E(2)) and progesterone (P) levels, thickness of endometrium, the zygote-and blastocyst-development rate between GnRH agonist and antagonist protocols (P>0.05). High quality embryo rate was higher in antagonist protocols, but there was no significant difference between two protocols. Implantation rate and clinical pregnant rate were significantly higher in antagonist protocol (15.82% and 30.26%, respectively) than in agonist protocol (5.26% and 10.64% respectively (P<0.05). It was concluded GnRH antagonist protocol probably improved the outcome of pregnancy of older patients with a history of multiple failure of IVF-ET in a GnRH protocol. | 18,846,352 |
Support vector machine-based classification of Alzheimer's disease from whole-brain anatomical MRI. | We present and evaluate a new automated method based on support vector machine (SVM) classification of whole-brain anatomical magnetic resonance imaging to discriminate between patients with Alzheimer's disease (AD) and elderly control subjects. We studied 16 patients with AD [mean age +/- standard deviation (SD) = 74.1 +/- 5.2 years, mini-mental score examination (MMSE) = 23.1 +/- 2.9] and 22 elderly controls (72.3 +/- 5.0 years, MMSE = 28.5 +/- 1.3). Three-dimensional T1-weighted MR images of each subject were automatically parcellated into regions of interest (ROIs). Based upon the characteristics of gray matter extracted from each ROI, we used an SVM algorithm to classify the subjects and statistical procedures based on bootstrap resampling to ensure the robustness of the results. We obtained 94.5% mean correct classification for AD and control subjects (mean specificity, 96.6%; mean sensitivity, 91.5%). Our method has the potential in distinguishing patients with AD from elderly controls and therefore may help in the early diagnosis of AD. | 18,846,369 |
Hodgkin lymphoma in Tyrol-a population-based study. | We aimed to analyze the epidemiology, clinical characteristics, and outcome of patients with Hodgkin lymphoma (HL) diagnosed in Tyrol. All patients with newly diagnosed HL between 1993 and 2005 were included in this study. Among the 158 cases included, nodular lymphocytic predominant HL (nodular paragranuloma) was identified in ten cases (6%) whereas the majority of patients had classical Hodgkin lymphoma. Age (p < 0.01), sex (p = 0.03), risk groups according to the German Hodgkin Study Group stratification (p < 0.01), and bone marrow infiltration (p < 0.01) were of prognostic significance considering overall survival (OS) whereas histological subtype and bulky disease were not. The 5- and 10-year OS rates for the total group were 89% and 85%, respectively. Notably, in patients with advanced-stage HL (n = 49), combined modality treatment resulted in significantly better OS than chemotherapy alone (p = 0.01). Three patients developed a second hematological malignancy and one patient developed breast cancer. However, five patients (3%) had a malignant hematological disorder before occurrence of HL. Concerning treatment-related toxicity, bleomycin-associated lung toxicity was observed in six (4%) patients and five (3%) developed lethal treatment-related infectious complications. Our results provide evidence that the incidence rate of HL in Tyrol is comparable to other Western countries. Modern risk-adapted treatment results in excellent long-term prognosis but may be complicated by serious nonhematological side effects, in particular, infections and bleomycin-induced lung toxicity. Furthermore, 3% of HL patients had an antecedent malignant hematological disease before occurrence of HL. | 18,846,373 |
Reactive oxygen species and inflammatory mediators enhance muscle spindles mechanosensitivity in rats. | We tested the hypothesis that reactive oxygen species (ROS) and inflammatory mediators affect transduction properties of muscle spindles. In rats, muscle spindles response to high-frequency vibration (HFV) was recorded before and after (1) injection of hydrogen peroxide (H2O2) in control rats and animals pre-treated with diclofenac (anti-inflammatory substance), (2) injection of bradykinin and (3) fatigue induced by muscle stimulation (MS) in control rats and rats receiving diclofenac, superoxide dismutase (SOD) or H2O2. Muscular oxidative stress and inflammation induced by H2O2 or MS were assessed by measurements of isoprostanes and IL-6 levels. In control rats, H2O2, bradykinin and MS significantly enhanced the HFV response. Pre-treatment with SOD abolished the post-MS-enhanced HFV response whereas diclofenac lowered the peak HFV response to MS and H2O2. H2O2 injection and MS elicited significant and similar increases in isoprostanes and IL-6. We report a direct modulation of muscle spindles mechanosensitivity by ROS and inflammatory mediators. | 18,846,383 |
A historical analysis of severe head injury. | Severe head injury (SHI) is a significant health, social and economic concern rendering a worldwide health problem. This retrospective study was designed to describe the features and outcomes of patients with SHI treated in a single neurosurgical unit (Hospital "12 de Octubre", Madrid, Spain) over a period approaching 13 years. The subjects enrolled were 895 patients (15 years or older) with non-missile SHI treated over the period January 1987 to August 1999, in whom a computerised tomography scan had been performed within the first 6 h of injury. We considered epidemiological, clinical, analytical, radiological and therapeutic data along with final patient outcomes. The overall mortality rate was 46.8% (419 patients). Of these 419 deaths, 177 (42.2%) occurred within the first 48 h of injury rendering an early death rate of 19.8% (177/895 patients). Despite overall mortality showing a clear decreasing trend by the end of the 1990s, proportions of early deaths (within the first 48 h of injury) dramatically rose in the last 3 years of the study. As a whole, an unfavourable outcome was recorded in 62.6% (560 patients). Despite continued efforts to improve the outcome of patients with SHI, the results of our study are pessimistic in that high mortality and unfavourable outcome rates were recorded in this large series of patients. Although overall mortality has diminished over the years, the number of early deaths has increased. | 18,846,394 |
Mechanisms of primary operative failure and results of remedial operation in patients with chronic pancreatitis. | Resection and drainage operations achieve long-term pain relief in approximately 85% of patients with chronic pancreatitis (CP). In patients who develop recurrent pain, a few data exist on the long-term results of remedial operations. Over an 18-year period (1988-2006), 316 patients with CP had primary resection or drainage operations at our institution. Thirty-nine developed recurrent pain and were treated by a remedial resection or drainage operation. Patient demographics, time to symptom recurrence, radiographic anatomic abnormalities, type of remedial operation, postoperative morbidity, and long-term outcomes were analyzed. Thirty-nine patients, 56% female with a mean age of 41 years (range 16-61 years) had either remedial resection: total pancreatectomy (TP; N = 8), pancreaticoduodenectomy (PD; N = 6), distal pancreatectomy (DP; N = 5), or drainage operation: duodenal preserving pancreatic head resection (DPPHR; N = 8), revision of pancreaticojejunostomy (N = 12). TP achieved pain relief in 88% with postoperative complications greater than or equal to grade III in 38% and diabetes in 100%. Drainage operations achieved pain relief in 67% of patients with postoperative complications greater than or equal to grade III in only 8%. Partial parenchymal resections (DPPHR, PD, DP) as a remedial procedure achieved pain relief <50% of the time. Drainage procedures, when anatomically feasible, are the preferred reoperation to treat patients with recurrent pain after failed primary operation for chronic pancreatitis. | 18,846,404 |
Isolated polyethylene exchange versus acetabular revision for polyethylene wear. | Polyethylene wear and osteolysis are not uncommon in THA mid- and long-term. In asymptomatic patients the dilemma faced by the orthopaedic surgeon is whether to revise the cup and risk damage to the supporting columns and even pelvic discontinuity or to perform isolated polyethylene exchange and risk a high rate of postoperative recurrent instability and dislocation that will necessitate further surgery. We retrospectively reviewed 62 patients (67 hips) who underwent revision arthroplasty for polywear and osteolysis. Thirty-six hips had isolated polyethylene exchange, while 31 had full acetabular revision. The minimum followup was 2 years (mean, 2.8 years; range, 2-5 years). Three of 36 hips with a retained cup grafted through the cup holes failed within 5 years due to acetabular loosening. One of 31 hips with full revision underwent re-revision for aseptic cup loosening at 5 months postoperatively. Although we do not recommend prophylactic revision of all cups for polywear and osteolysis, the patient may be warned of the possibility of an approximate 10% failure rate when retaining the acetabular component. We do, however, advocate cup extraction in the following situations: damage to the locking mechanism, erosion of the femoral head through the liner and into the cup damaging the metal, and a malpositioned component that may jeopardize the stability of the revision. Level II, prognostic study. See the Guidelines for Authors for a complete description of levels of evidence. | 18,846,409 |
A perspective on Peter Mitchell and the chemiosmotic theory. | In 1991 Peter Mitchell wrote a last article that summarised his views on the origin, development and current status of his chemiosmotic ideas. I here review some of his views of that time on structures and mechanisms of several key bioenergetic components in relation to the subsequent advances that have been made. | 18,846,415 |
Predictors of sexual debut at age 16 or younger. | The present study examined the extent to which variables within the self system (i.e., symptoms of alcohol dependence and conduct disorder, gender, race, and metropolitan status) and the familial system (i.e., having an alcohol dependent biological parent or second-degree relative, religious background, educational background of parents, and being born to a teenage mother) were associated with sexual debut at 16 years old or earlier. Participants were 1,054 biological relatives, aged 18-25 years, of alcohol dependent probands who participated in the Collaborative Study on the Genetics of Alcoholism project. Comparison participants (N = 234) without alcohol dependent biological parents were also evaluated. Clinical and sociodemographic variables were assessed by structured, personal interviews. Parental history of alcohol dependence was evaluated by direct interview of parents in most cases and family history in uninterviewed parents. In a multivariate survival analysis, increased risk of becoming sexually active at 16 years of age or earlier was significantly associated with 6 of the 10 predictor variables, including race, one or more alcohol dependence symptoms, and/or one or more conduct disorder symptoms. Having an alcohol dependent biological parent or second-degree relative (e.g., aunt, uncle, or grandparent), educational background of mother, and being born to a teenage mother were also significantly associated with increased risk. These results provide evidence that specific variables in the self and familial systems of influence are important in predicting sexual debut at 16 years old or earlier. | 18,846,417 |
Mediators of neighborhood influences on externalizing behavior in preadolescent children. | This study tested a mediation model of neighborhood influences on children's externalizing behavior. In the proposed model, neighborhood disadvantage, ethnic heterogeneity, and low residential stability affect children's behavior indirectly through their impact on neighborhood social processes, which in turn influence parenting and deviant peer affiliations. A community sample of 704 preadolescents (76% African American, 22% Caucasian) and their parents and teachers provided information for the study. Neighborhood concentrated poverty, derived from the 2000 U.S. Census, was positively associated with children's externalizing behavior. This effect was fully mediated by neighborhood social processes and parenting quality, while deviant peer affiliations made independent contributions to problem behavior. The final mediation model explained children's externalizing behavior equally well across gender and ethnicity, suggesting the presence of universal processes. | 18,846,420 |
Trichloroethylene cometabolic degradation by Rhodococcus sp. L4 induced with plant essential oils. | Cometabolic degradation of TCE by toluene-degrading bacteria has the potential for being a cost-effective bioremediation technology. However, the application of toluene may pose environmental problems. In this study, several plant essential oils and their components were examined as alternative inducer for TCE cometabolic degradation in a toluene-degrading bacterium, Rhodococcus sp. L4. Using the initial TCE concentration of 80 microM, lemon and lemongrass oil-grown cells were capable of 20 +/- 6% and 27 +/- 8% TCE degradation, which were lower than that of toluene-grown cells (57 +/- 5%). The ability of TCE degradation increased to 36 +/- 6% when the bacterium was induced with cumin oil. The induction of TCE-degrading enzymes was suggested to be due to the presence of citral, cumin aldehyde, cumene, and limonene in these essential oils. In particular, the efficiency of cumin aldehyde and cumene as inducers for TCE cometabolic degradation was similar to toluene. TCE transformation capacities (T (c)) for these induced cells were between 9.4 and 15.1 microg of TCE mg cells(-1), which were similar to the known toluene, phenol, propane or ammonia degraders. Since these plant essential oils are abundant and considered non-toxic to humans, they may be applied to stimulate TCE degradation in the environment. | 18,846,429 |
A comparative study of noise pollution levels in some selected areas in Ilorin Metropolis, Nigeria. | The noise pollution is a major problem for the quality of life in urban areas. This study was conducted to compare the noise pollution levels at busy roads/road junctions, passengers loading parks, commercial, industrial and residential areas in Ilorin metropolis. A total number of 47-locations were selected within the metropolis. Statistical analysis shows significant difference (P < 0.05) in noise pollution levels between industrial areas and low density residential areas, industrial areas and high density areas, industrial areas and passengers loading parks, industrial areas and commercial areas, busy roads/road junctions and low density areas, passengers loading parks and commercial areas and commercial areas and low density areas. There is no significant difference (P > 0.05) in noise pollution levels between industrial areas and busy roads/road junctions, busy roads/road junctions and high density areas, busy roads/road junctions and passengers loading parks, busy roads/road junctions and commercial areas, passengers loading parks and high density areas, passengers loading parks and commercial areas and commercial areas and high density areas. The results show that Industrial areas have the highest noise pollution levels (110.2 dB(A)) followed by busy roads/Road junctions (91.5 dB(A)), Passengers loading parks (87.8 dB(A)) and Commercial areas (84.4 dB(A)). The noise pollution levels in Ilorin metropolis exceeded the recommended level by WHO at 34 of 47 measuring points. It can be concluded that the city is environmentally noise polluted and road traffic and industrial machineries are the major sources of it. Noting the noise emission standards, technical control measures, planning and promoting the citizens awareness about the high noise risk may help to relieve the noise problem in the metropolis. | 18,846,431 |
Hereditary haemochromatosis gene (HFE) H63D mutation shows an association with abnormal sperm motility. | The aim of this study was to screen infertile men for HFE H63D mutation in correlation with clinical characteristics of infertile men (sperm concentration, sperm motility, morphology, testicular volume, Follicle Stimulating Hormone (FSH), Luteinizing Hormone (LH) and total Testosterone levels) and find out if the HFE H63D mutation has an effect on male infertility. After excluding hormonal treatment, any scrotal pathology, having any systemic diseases such as diabetes mellitus, sickle cell anemia and microdeletions of the Y chromosome, a total of 148 infertile men with age range between 17 and 52-years-old (average age 29.6 +/- 7.2) were enrolled into the study. Our analysis indicates that the mean FSH levels are significantly higher (6.3 +/- 4.6 mIU/ml, P = 0.03), whereas sperm motility is significantly lower (36.6 +/- 28.1%, P = 0.01) in the infertile men with the HFE H63D mutation compared with subjects lacking this mutation. Comparison of allele frequencies of the infertile men with Ts < 50% versus the infertile men with Ts > 50% revealed a significant difference as expected (P = 0.001, OR = 0.14, %95 CI = 0.04-0.44). Comparison of allele frequencies of infertile men with abnormal sperm motility versus infertile men with normal sperm motility revealed a highly significant difference (P = 0.005, OR = 3.11, %95 CI = 1.41-6.86). Thus, the HFE H63D mutation seems to be an important risk factor for impaired sperm motility and is clinically associated with male infertility. | 18,846,434 |
Escape behaviour elicited by a visual stimulus. A comparison between lateralised and non-lateralised female topminnows. | Studies over the past 30 years suggest that functional lateralisation occurs in many animal species. Preferential eye use is ubiquitous among fish, and recently some advantages of being lateralised have been reported in the golden topminnow, Girardinus falcatus, using fish from lines selected for high or low degrees of behavioural lateralisation. In the present paper we investigated whether non-lateralised fish differed from lateralised fish in escape behaviour elicited by a potentially dangerous stimulus. A total of 56 female topminnows were observed when swimming in an unknown environment in which the shape of a predator was presented on either the right or the left side of the visual field. We found no side differences in latency and efficiency of escape reaction and on the whole non-lateralised fish escaped as quickly as lateralised individuals. We discuss our results in the light of recent findings suggesting that the development of lateralisation in the fast escape response in fish may be controlled by a mechanism distinct from that controlling the asymmetric placement of most other cognitive functions. | 18,846,442 |
Mitral valve surgery--a Scandinavian perspective. | During the last three decades, the most prevalent surgical mitral valve disease in Scandinavia has changed from the sequelae of rheumatic fever to the mitral valve pathologies related to ischemic heart disease. Also, the total number of patients in need of a mitral valve procedure is increasing. For several of the patients with ischemic mitral valve disease, the natural prognosis of their disease is dismal. However, there are several uncertainties as to whether or not a surgical procedure can improve the life expectancies of these patients. Also, the procedures of choice for patients with ischemia related "functional mitral valve disease" is a long standing controversy. In this issue of "Scandinavian Cardiovascular Journal" we present the rationale and protocol for the "MoMIC" trial, a randomized multicenter study aiming to clarify whether revascularization alone or a combined revascularization and mitral valve annuloplasty is the treatment of choice for patients with ischemia related moderate mitral regurgitation. | 18,846,476 |
[Damage control orthopaedics in polytraumatised patients with lower leg injuries]. | In polytraumatised patients, fracture management depends on the overall injury severity. For decision making, patients are grouped in one of four categories (STABILE, BORDERLINE, INSTABLE and IN EXTREMIS). STABILE patients should and BORDERLINE patients may undergo primary definitive fracture stabilisation; in contrast, this is not recommended for INSTABLE or IN EXTREMIS patients. The marginal soft tissue envelope of the tibia predisposes for open fractures, compartment syndrome, and wound infections. Therefore the management of lower leg injuries is demanding, especially in polytraumatised patients. Bilateral tibia fractures and ipsilateral tibia and femur fractures represent a special entity. For these injuries special algorithms, which consider the soft tissue status of the tibia and the overall injury severity, have been developed. The indication for fasciotomy covers a wide field and may be performed prophylactically. The decision for amputation is based on the patient's general condition and the soft-tissue and neurovascular status. Scoring systems are useful for decision making, however individual decisions should be made. | 18,846,483 |
[Webers experiments regarding the stabilising effect of atmospheric pressure on the hip joint - a historical and experimental retrospect]. | The stabilising effect of atmospheric pressure on the hip joint was first described by the brothers Eduard and Wilhelm Weber in 1836. Later in 1837, they conducted an experiment in which they examined a weight-bearing cadaveric hip joint in an evacuable container and could repeatedly demonstrate dislocation of the femur head due to the significant reduction of surrounding pressure and its repositioning by normalisation of the pressure. In our study we aimed to honour the contribution of the Weber brothers, to reflect on the historical argument about the hip stabilising effect of atmospheric pressure they initiated, to repeat the famous experiment they did in 1837 using advanced sensors and radiological equipment and to demonstrate the consequences of the effect on total hip arthroplasty. A weight-bearing human cadaveric hip joint was placed in a radiolucent evacuable container, in which the pressure was reduced with a vacuum pump and normalised by opening a valve. Pressure and dislocation distance were measured continuously by sensors. The state of the hip joint was documented both by X-ray as well as by permanent fluoroscopy with video recording. Conforming to the experiments published in 1837 we demonstrated dislocation of the hip joint as a result of a significant reduction of pressure. Normalisation of the pressure caused joint reduction. The ability of the cadaveric hip to bear weight depended to a great extent on its quality. Reduction of the pressure harmed the cadaveric hip and reduced the number of possible experiments. The stabilising effect of atmospheric pressure on the hip joint is a fact, which was proved in 1836/37 by the Weber brothers, who conducted convincing experiments with human cadaveric hip joints. Nevertheless, the investigation into this relationship continues until today. We repeated and reproduced their experiment published in 1837 which irrefutably proved the stabilising effect of atmospheric pressure on the hip joint. The surgical application is of the utmost importance in the field of hip arthroplasty. Careful handling and reconstruction of the capsula, the use of size-adapted large hip balls as well as the intra-articular drainage provide the basis for maintaining the optimal mechanical environment and avoiding postoperative dislocation. Due to the variation in quality and anatomic characteristics of cadaveric hip specimens, we decided to use standardised model joints for further experiments. | 18,846,493 |
Roscovitine up-regulates p53 protein and induces apoptosis in human HeLaS(3) cervix carcinoma cells. | Exposure of human HeLaS(3) cervix carcinoma cells to high doses of conventional cytostatic drugs, e.g. cisplatin (CP) strongly inhibits their proliferation. However, most cytostatic agents are genotoxic and may generate a secondary malignancy. Therefore, therapeutic strategy using alternative, not cytotoxic drugs would be beneficial. Inhibition of cyclin-dependent kinases (CDKs) by pharmacological inhibitors became recently a promising therapeutic option. Roscovitine (ROSC), a selective CDK inhibitor, efficiently targets human malignant cells. ROSC induces cell cycle arrest and apoptosis in human MCF-7 breast cancer cells. ROSC also activates p53 protein. Activation of p53 tumor suppressor protein is essential for induction of apoptosis in MCF-7 cells. Considering the fact that in HeLaS(3) cells wt p53 is inactivated by the action of HPV-encoded E6 oncoprotein, we addressed the question whether ROSC would be able to reactivate p53 protein in them. Their exposure to ROSC for 24 h induced cell cycle arrest at G(2)/M and reduced the number of viable cells. Unlike CP, ROSC in the used doses did not induce DNA damage and was not directly cytotoxic. Despite lack of detectable DNA lesions, ROSC activated wt p53 protein. The increase of p53 levels was attributable to the ROSC-mediated protein stabilization. Further analyses revealed that ROSC induced site-specific phosphorylation of p53 protein at Ser46. After longer exposure, ROSC induced apoptosis in HeLaS(3) cells. These results indicate that therapy of HeLaS(3) cells by ROSC could offer an advantage over that by CP due to its increased selectivity and markedly reduced risk of generation of a secondary cancer. | 18,846,503 |
Quantitative phosphoproteome analysis of a mouse liver cell line reveals specificity of phosphatase inhibitors. | The liver is a central organ involved in many aspects of physiology and disease. Signaling properties of hepatocytes, the main liver cell type, are of special interest in metabolic diseases and in regeneration. For this reason we investigated the phosphoproteome of the mouse liver cell line Hepa1-6 by stable isotope labeling by amino acids in cell culture (SILAC) and high resolution MS. Using stringent statistical evaluation criteria, we obtained 5433 phosphorylation sites on 1808 proteins. The phosphoproteome encompasses all major protein classes, including a large number of transcription factors. We compared control and phosphatase inhibitor treated cells by SILAC. This enabled ready identification of in vivo phosphorylation sites by sequencing the more abundant, inhibitor induced version of the peptide while still observing the endogenous version. We employed a mixture of pervanadate for blocking protein tyrosine phosphatases (PTPs) and calyculin A and deltamethrin for blocking the activities of serine/threonine phosphatases. Interestingly, these commonly used inhibitors in standard concentrations affected only 28% of the phosphopeptides by at least two-fold. The unaffected sites may be substrates of phosphatases that are not efficiently inhibited, have slow kinetic or sites that are almost stoichiometric in normally growing cells. Finally, we devised a triple labeling strategy comprising control cells, stimulated cells, and phosphatase treated cells to derive an upper bound on phosphorylation occupancy. | 18,846,507 |
Proteomics and phosphoproteomics for the mapping of cellular signalling networks. | Proteomics is transitioning from inventory mapping to the mapping of functional cellular contexts. This has been enabled by progress in technologies as well as conceptual strategies. Here, we review recent advances in this area with focus on cellular signalling pathways. We discuss genetics-based methods such as yeast two hybrid methods as well as biochemistry-based methods such as two-dimensional gel electrophoresis, quantitative proteomics, interaction proteomics, and phosphoproteomics. A central tenet is that by its ability to capture dynamic changes in protein expression, localisation and modification modern proteomics has become a powerful tool to map signal transduction pathways and deliver the functional information that will promote insights in cell biology and systems biology. | 18,846,508 |
Autonomic innervation of the developing heart: origins and function. | Maintenance of homeostatic circulation in mammals and birds is reliant upon autonomic innervation of the heart. Neural branches of mixed cellular origin and function innervate the heart at the arterial and venous poles as it matures, eventually coupling autonomic output to the cardiac components, including the conduction system. The development of neural identity is controlled by specific networks of genes and growth factors, whereas functional properties are governed by the use of different neurotransmitters. In this review, we summarize briefly the anatomic arrangement of the vertebrate autonomic nervous system and describe, in detail, the innervation of the heart. We discuss the timing of cardiac innervation in the chick and mouse, emphasizing the relationship of the cardiac neural networks to the anatomical structures within the heart. We also discuss the variable contribution of the neural crest to vagal cardiac nerves, and summarize the main neurotransmitters secreted by the developing sympathetic and parasympathetic autonomic divisions. We provide an overview of the main growth factor and gene families involved in neural development, discussing how these factors may impact upon the development of cardiac abnormalities in congenital syndromes associated with autonomic dysfunction. | 18,846,544 |
Shoes influence lower limb muscle activity and may predispose the wearer to lateral ankle ligament injury. | Lateral ankle ligaments are injured by hyperinversion of the foot. Foot position is controlled by the lower limb muscles. Awareness of foot position is impaired by wearing shoes. We aimed to determine the influence of wearing shoes upon muscle activity. Sixty-two healthy subjects underwent the same measurements, barefoot and with standardized shoes in a random order. Electromyography (EMG) was recorded from the peroneus longus muscle in response to sudden and unanticipated inversion of the ipsilateral foot. Following foot inversion, the EMG signal showed an initial peak muscle contraction followed by a sustained smaller contraction. Both changes were significantly greater in shoes compared to the barefoot condition for all tested degrees of inversion. Muscle contraction following sudden inversion of the foot was significantly greater when wearing shoes. This greater muscular contraction may be an intrinsic mechanism to oppose the increased moment created by the inverted foot/shoe condition, and hence, may counter balance the increased tendency to injure the lateral ankle ligaments created by wearing shoes. | 18,846,547 |
Chronic cough and tonsillar hypertrophy: a case series. | Two patients with intractable chronic cough were found to have tonsillar tissue impinging on their epiglottis. In both case, tonsillectomy was curative. The observations in these patients are consistent with a previous report indicating chronic cough from the uvula in contact with the epiglottis with cough cessation following uvulectomy. | 18,846,560 |
Reproducibility of spirometry during cystic fibrosis pulmonary exacerbations. | To compare the within day variation of spirometry between hospital admission, discharge, and outpatient follow up among children with cystic fibrosis (CF) hospitalized for a pulmonary exacerbation. Within day variation of spirometry will be greater at hospital admission than at hospital discharge or outpatient follow up. We performed a retrospective review of spirometry data for all patients with CF >or=6 years old admitted to our pediatric CF center for a pulmonary exacerbation in 2004 or 2005. For patients who had previously performed spirometry successfully, measurements were used from one admission only during 2004-2005 if the spirometry occurred within 3 days of hospital admission, 3 days of discharge, or at a follow up clinic visit when well. We compared the within day coefficients of variation (CV) for FVC, FEV(1), and FEF(25-75) between time points using the Wilcoxon signed rank-test. We also determined the change in spirometry that is likely to be beyond measurement variability during inpatient treatment of a pulmonary exacerbation. Spirometry data were available from 40 subjects at admission and follow up and 35 at hospital discharge. There was no significant difference in CV at admission, discharge, and follow up for FVC, FEV(1), or FEF(25-75). The mean (SD) CV was 3.1% (2.7) for FVC, 3.2% (2.1) for FEV(1), and 9.7% (7.0) for FEF(25-75) at admission, 2.8% (2.2) for FVC, 3.1% (2.1) for FEV(1), and 8.1% (6.7) for FEF(25-75) at discharge, and 2.7% (1.7) for FVC, 2.8% (2.0) for FEV(1), and 8.4% (7.8) for FEF(25-75) at follow up. These are similar to previous reports of outpatients with CF. The improvement in spirometry that exceeded measurement variability for our cohort was 80 ml for FVC, 70 ml for FEV(1), and 220 ml/sec for FEF(25-75). The presence of an acute pulmonary exacerbation in children and adolescents with CF does not substantially contribute to the within day variation in spirometry. Within day variation of spirometry for children with CF during pulmonary exacerbations is similar to previously reported values from clinically stable CF patients. | 18,846,562 |
Soy lecithin supplementation alters macrophage phagocytosis and lymphocyte response to concanavalin A: a study in alloxan-induced diabetic rats. | Dietary soy lecithin supplementation decreases hyperlipidemia and influences lipid metabolism. Although this product is used by diabetic patients, there are no data about the effect of soy lecithin supplementation on the immune system. The addition of phosphatidylcholine, the main component of lecithin, to a culture of lymphocytes has been reported to alter their function. If phosphatidylcholine changes lymphocyte functions in vitro as previously shown, then it could also affect immune cells in vivo. In the present study, the effect of dietary soy lecithin on macrophage phagocytic capacity and on lymphocyte number in response to concanavalin A (ConA) stimulation was investigated in non-diabetic and alloxan-induced diabetic rats. Supplementation was carried out daily with 2 g kg(-1) b.w. lecithin during 7 days. After that, blood was drawn from fasting rats and peritoneal macrophages and mesenteric lymph node lymphocytes were collected to determine the phospholipid content. Plasma triacylglycerol (TAG), total and HDL cholesterol and glucose levels were also determined. Lymphocytes were stimulated by ConA. The MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) dye reduction method and flow cytometry were employed to evaluate lymphocyte metabolism and cell number, respectively. Soy lecithin supplementation significantly increased both macrophage phagocytic capacity (+29%) in non-diabetic rats and the lymphocyte number in diabetic rats (+92%). It is unlikely that plasma lipid levels indirectly affect immune cells, since plasma cholesterol, TAG, or phospholipid content was not modified by lecithin supplementation. In conclusion, lymphocyte and macrophage function were altered by lecithin supplementation, indicating an immunomodulatory effect of phosphatidylcholine. | 18,846,580 |
beta'-Hydroxy-alpha,beta-unsaturated ketones: A new pharmacophore for the design of anticancer drugs. Part 2. | Novel antiproliferative beta'-acyloxy-alpha,beta-unsaturated ketones were obtained by means of an iron(III)-catalyzed multicomponent domino process (ABB' 3CR). The most active derivatives displayed GI(50) values in the range of 0.5-3.9 muM against a panel of representative human solid tumor cell lines: A2780, SW1573, HBL-100, T-47D and WiDr. Analysis of cells following 24 h exposure to these drugs showed cell cycle arrest in the S and G(2)/M phase, in a dose-dependent manner. Our data indicate that the beta'-acyloxy-alpha,beta-unsaturated ketones cause permanent damage to the cells and induce apoptosis. | 18,846,591 |
Interaction of NO2 with model NSR catalysts: metal-oxide interaction controls initial NOx storage mechanism. | Using scanning tunneling microscopy (STM), molecular-beam (MB) methods and time-resolved infrared reflection absorption spectroscopy (TR-IRAS), we investigate the mechanism of initial NO(x) uptake on a model nitrogen storage and reduction (NSR) catalyst. The model system is prepared by co-deposition of Pd metal particles and Ba-containing oxide particles onto an ordered alumina film on NiAl(110). We show that the metal-oxide interaction between the active noble metal particles and the NO(x) storage compound in NSR model catalysts plays an important role in the reaction mechanism. We suggest that strong interaction facilitates reverse spillover of activated oxygen species from the NO(x) storage compound to the metal. This process leads to partial oxidation of the metal nanoparticles and simultaneous stabilization of the surface nitrite intermediate. | 18,846,595 |
Efficient synthesis of dimethyl ether over HZSM-5 supported on medium-surface-area beta-SiC foam. | In this study, we aimed to produce a highly selective and stable catalyst for the production of dimethyl ether by methanol dehydration. The activities were compared of different active phases of the employed system, zeolite HZSM-5 or gamma-alumina, supported on silicon carbide as foam, and it was found that the supported zeolite catalysts are more active than and as selective as the alumina-based catalysts. The as-prepared zeolite/SiC composites reveal good stability in long-term tests in the presence or absence of steam. The high stability is attributed to the presence of highly dispersed micrometer-sized zeolite particles, which make the active sites more accessible to the reactants and promote the quick transfer of the desired product, dimethyl ether, out of the catalyst bed, minimizing deactivation of the catalyst. | 18,846,596 |
[Abdominal compartment syndrome]. | Abdominal compartment syndrome is a potentially lethal condition caused by any event that produces intra-abdominal hypertension; the most common cause is blunt abdominal trauma Increasing intra-abdominal pressure causes progressive hypoperfusion and ischemia of the intestines and other peritoneal and retroperitoneal structures. Pathophysiological processes may lead to translocation of bacteria from the gut and intestinal edema, predisposing patients to multiorgan dysfunction syndrome. The consequences of abdominal compartment syndrome are profound and affect many vital body systems. Hemodynamic, respiratory, renal, and neurological abnormalities are hallmarks of abdominal compartment syndrome. Medical management consists of urgent decompressive laparotomy. | 18,846,692 |
[Cystopericystectomy for the treatment of hepatic hydatid disease]. | Hepatic hydatid disease is current problem in Bulgaria as the country in endemic region. The treatment include PAIR, various type surgical procedures and medical therapy. Surgical treatment is conductive. Cystopericystectomy is one of radical procedures. The aim of this study is to present the experience of Department of General and Liver-Pancreatic Surgery in Uiversity Hospital "Alexandrovska", Sofia with cystopericystectomy. During the period of 18-years (1988-2005) done 90 cystopericystectomies on the 79 patients--57 (72.15%) female and 22 (27.85%) male. Diagnosis has become easier with advances in ultrasonic imaging, immunological tests and CT scanning. The cysts ware localised in left lobe--56 (62.2%) and right lobe--34 (37.8%). There was complication in 4 (5.0%) of patients. Median postoperative stay is 10.3 days. There wasn't reoperacions and lethal outcome. Cystopericystectomy is difficult operative procedure, but it followed with better results. It's necessary strictly abidance of the evidences. | 18,846,694 |
[Indirect prenatal molecular diagnostic of haemophilia A and B]. | Haemophilia A (HA) and B (HB) are the most common inherited bleeding diseases. HA and HB are X-linked recessive disorders caused by mutation in the factor VIII gene which maps to Xq28 and factor IX located at Xq27, respectively; resulting in absence or deficiency of these proteins. Several mutations have been reported as responsible for the disturbance of these genes; therefore, the use of direct molecular techniques to analyze the carrier status of women and their affected fetuses in not easy to perform. Thus, gene linked polymorphisms analysis is the most convenient molecular test since it is independent from the nature of the mutation, allowing the identification of the mutant X chromosome by following its segregation along the pedigree. The main objective of this research was to perform the molecular diagnosis of HA or HB carrier status in pregnant women and male fetuses affected or not, who were referred to the Medical Genetic Unit of the University of Zulia (UGM-LUZ), Maracaibo, Venezuela. Molecular analysis for HA and HB was performed in 32 DNA samples from 8 pregnant women, 8 fetuses, 8 affected and 8 healthy males. Using the Polymerase Chain Reaction (PCR), a 142 bp (bases pairs) fragment, which corresponds to intron 18 of the Factor VIII gene, was amplified. This fragment has a restriction polymorphism for the enzyme Bcl I. Additionally, a Duplex PCR was performed for the STRs (short tandem repeat) of introns 13 and 22 of the same gene. On the other hand, Hinf I, Xmn I y Taq I polymorphism in the factor IX gene were also amplified, so, we were able to build the haplotypes for each one of the key members in the families affected. The latter, allowed us to identify, in five of the eight cases, the mutant X chromosome responsible of HA and HB, thus, prenatal diagnosis was possible with the following results: three healthy males fetuses, two affected males fetuses with HA and three females fetuses. | 18,846,770 |
Spot urine protein: creatinine ratio versus 24 hour urine protein at various levels of GFR patients referred to a tertiary care hospital of Pakistan. | To determine the correlation of "random single voided urine protein: creatinine ratio" to "twenty four hour urine protein" at different levels of glomerular filtration rate (GFR) in Pakistani population. A total of 107 patients were included in this cross section study. Patients were divided into five groups according to the GFR. Spot urine protein: creatinine ratio and 24 hour urine protein was measured by the standard methods. The correlation coefficient ( r) between the two was calculated in each group separately. The GFR in groups 1 to 5 was > or =90, 60-89, 30-59, 15-29, and <15 ml/minute/1.73 m2 respectively. In group one correlation coefficient "r" was 0.96, in group two "r" was 0.81, in group three "r" was 0.94, in group four "r" was 0.82 and in group five "r" was 0.80. "Random single voided urine protein: creatinine ratio" may be used as an alternative to "24 hour urine collection for protein" at all levels of GFR in Pakistani population. | 18,846,792 |
Perinatal outcomes in pregnancy with asthma. | To examine the relationship between asthmatic pregnancies and selected maternal and neonatal outcomes in a representative cohort. A retrospective cohort study was conducted at the Aga Khan University Hospital during the year 2004. A random selection was made of 65 asthmatic and 63 non-asthmatic singleton births. The neonatal outcomes studied were birth weight, premature birth and Apgar scores at 1 and 5 minutes. The maternal outcomes studied were number of hospital admissions, and number of documented UTI during the studied pregnancy and past history of abortions and stillbirths. The mean age of asthmatics and nonasthmatics were 28.0 +/- 4.9 years and 27.7 +/- 3.6 years respectively. The average parity among asthmatic women was 2.97 while that in controls was 2.57 (p < 0.137). Neonates born to asthmatic mothers had shorter mean gestational age with increased risk of premature birth and lower Apgar scores. Asthmatic mothers had a greater risk of abortions and low birth weight babies. They also had higher rates of UTIs and hospital admissions. Asthmatic pregnancies are more likely to result in abortion, premature delivery and low birth weight babies. The asthmatic pregnancies were also linked with higher rates of maternal UTI. Thcrefore a more vigilant monitoring is required in asthmatic pregnancies. | 18,846,809 |
A comparison of the efficacy of doramectin, closantel and levamisole in the treatment of the 'oriental eye fluke', Philophthalmus gralli, in commercially reared ostriches (Struthio camelus). | Commercially reared ostriches at Msengi farm situated in the Chinhoyi area of Mashonaland West province in Zimbabwe were found to be infected with the 'oriental eye fluke', Philopthalmus gralli, in 2001. This was the ist record of the fluke in Zimbabwe. Trials were conducted to identify a suitable drug for the treatment of this fluke. A total of 12 ostriches confirmed to be infected with the fluke through clinical examination of the eyes and identification of the fluke were randomly divided into 3 equal groups, with each group receiving a different treatment protocol. The 3 drugs used were doramectin, levamisole and closantel. Each of the drugs was used in combination with chloramphenicol as an eye ointment. Levamisole was administered topically into the eye whereas doramectin and closantel were administered parenterally as an intramuscular injection. The results indicated a positive response in levamisole-treated birds but there were no noticeable responses to doramectin and closantel treatments. | 18,846,856 |
Castlemans disease in HIV infected patient from eastern India. | Castlemans disease is a rare lymphoproliferative disorder. We report a patient of Castlemans disease with advanced HIV infection who responded well to conventional HAART. This case is interesting because of the rarity of the disease in the eastern part of India and its good out come with antiretroviral therapy. | 18,846,911 |
Alkaptonuria and intramedullary calcification. | Alkaptonuria is a rare disorder of metabolism caused by deficiency of homogentisic acid oxidase enzyme and characterized by triad of homogentisic aciduria (dark urine), relentlessly progressive arthritis and ochronosis. We have documented a case with typical features of alkaptonuria along with intramedullary calcification which has not been reported in the literature before. | 18,846,913 |
Diagnostic algorithm and therapeutic options in chronic heart failure: updated review of clinical practice guidelines. | The development of diagnostic and therapeutic algorithms is becoming more and more popular in medicine. Their advantage is simplicity which enables wide use in everyday medical practice. The algorithms may have limitations mainly due to simplifications, which not always appear to be helpful in solving complex clinical problems of an individual patient. To serve as a "signpost" in clinical practice, the algorithm should be worked out strictly according to the appropriately interpreted data obtained from reliable, current and published medical evidence. This aim is achieved by clinical practice guidelines, being developed by scientific societies. The present paper deals with diagnostic and therapeutic algorithms in chronic heart failure based on the current clinical practice guidelines. The current guidelines by the European Society of Cardiology have been compared with similar documents issued by the American College of Cardiology/American Heart Association, the Heart Failure Society of America and the Canadian Cardiovascular Society. Similarities and divergences between the guidelines of different societies in respect of treatment for chronic heart failure have been discussed. The detailed description of their role in the treatment has been provided for: non-pharmacological measures (guidelines for lifestyle), drug therapy (angiotensin-converting enzyme inhibitors, beta-adrenolytics, aldosterone receptor antagonists, angiotensin receptor blockers, cardiac glycosides and diuretics), implantation of cardioverter-defibrillators and (or) resynchronization device, mechanical support and surgical treatment. The paper also focuses on diagnostic problems and treatment modalities for heart failure with a preserved systolic function of the left ventricle. | 18,846,984 |
[Etiology of Dupuytren's contracture]. | Dupuytren's contracture is a connective tissue disorder characterized by contractile palmar aponeurosis leading to shortening and progressive digital flexion deformity. Various investigators have proposed many theories and documented several findings regarding the aetiology of Dupuytren's contracture. However, none of them explains the causes well enough. Most studies have found relationships between the disorder and manual labor, previous hand injures, genetic susceptibility, diabetes mellitus, epilepsy, high cholesterol level profile and intake of either alcohol or tobacco. However, according to others, the evidence on risk factors associated with certain lifestyles has been conflicting. This article reviews the most common theories regarding the aetiology of Dupuytren's contracture such as genetic, microinjury, immunological, toxic and ischaemic theories. | 18,847,012 |
[Modular short-stem prosthesis in total hip arthroplasty--preliminary report]. | Total hip arthroplasty has become one of the most succesful procedure in orthopaedic surgery. More and more active, young patients undergo primary hip replacement. Bone stock preservation is crucial when performing THR in this group of patients. The short stem design allows a methaphyseal intratrochanteric multipoint, strong primary fixation which is very important for this group of patients. The goal is to save bone stock for the revision operation. This study presents early results of Metha short stems prosthesis. Between April 2006-December 2007, 58 short stem (Metha) were implanted. The Harris Hip Score improved from a mean 64.3 before to 89.7 at follow-up. The Metha stem may not be indicated for every hip diseases. There were only two fractures of femur without any further problems. Despite the short follow-up, Metha prosthesis already represent a valuable alternative for younger patients. | 18,847,014 |
[Effects of massage on delayed-onset muscle soreness]. | Delayed onset muscle soreness (DOMS) is the pain or discomfort often felt 12 to 24 hours after exercising and subsides generally within 4 to 6 days. Once thought to be caused by lactic acid buildup, a more recent theory is that it is caused by inflammatory process or tiny tears in the muscle fibers caused by eccentric contraction, or unaccustomed training levels. Exercises that involve many eccentric contractions will result in the most severe DOMS. Fourteen healthy men with no history of upper arm injury and no experience in resistance training were recruited. The mean age, height, and mass of the subjects were 22.8 +/- 1.2 years, 178.3 +/- 10.3 cm, and 75.0 +/- 14.2 kg, respectively. Subjects performed 8 sets of concentric and eccentric actions of the elbow flexors with each arm according to Stay protocol. One arm received 10 minutes of massage 30 minutes after exercise, the contralateral arm received no treatment. Measurements were taken at 9 assessment times: pre-exercise and postexercise at 10 min, 6, 12, 24, 36, 48, 72 and 96 hours. Dependent variables were range of motion, perceived soreness and upper arm circumference. There was noticed difference in perceived soreness across time between groups. The analysis indicated that massage resulted in a 10% to 20% decrease in the severity of soreness, but the differences were not significant. Difference in range of motion and arm circumference was not observed. Massage administered 30 minutes after exercises could have a beneficial influence on DOMS but without influence on muscle swelling and range of motion. | 18,847,018 |
Organized extracurricular activities of Canadian children and youth. | This article presents rates of participation in organized extracurricular activity by Canadian children and youth aged 6 to 17 years, and examines how these rates vary by sociodemographic and socio-economic characteristics. The data are from Cycle 4 of the National Longitudinal Survey of Children and Youth (2000/2001). The majority of children and youth (86%) participated in at least one extracurricular activity. Girls were more likely than boys to be involved in non-sport activities and in clubs or community groups. Young children who lived in urban areas and those who lived with two parents had relatively high rates of participation in extracurricular activities. Participation rose with family income for children aged 6 to 13, but not for 14- to 17-year-olds. Children of all ages in the Western provinces had high participation rates in each type of activity; rates tended to be low in Quebec. | 18,847,147 |
Radiological findings in sarcoidosis. | Sarcoidosis is a multisystemic disorder of unknown cause that primarily affects the lungs. The diagnosis is based on the clinical manifestations, radiological findings and histological examination. To review and illustrate the typical and atypical radiological findings of sarcoidosis in the chest. We analyzed the radiographic thoracic findings of all patients who had biopsy-proven sarcoidosis over the last 10 years. There were 100 consecutive patients (36 men and 64 women, age 20-84 years) with an established diagnosis of sarcoidosis. Thoracic lymphadenopathy was detected in 89 patients (89%). Lung parenchyma involvement was found in 60 patients. These changes were variable and included: ground-glass attenuation (n=39), multiple small nodules (n=44) and irregular thickening of the interlobular septa (n=16). Larger nodules (1-3 cm) were identified in 12 patients and frank consolidations were seen in 12 patients. Pleural thickening with subpleural nodules was identified in 17 patients. Sarcoidosis has a wide variety of radiological manifestations in the chest. Familiarity with the various radiographic findings is important for diagnosis and management. | 18,847,152 |
Correction of pre-steady-state KIEs for isotopic impurities and the consequences of kinetic isotope fractionation. | We show, both experimentally and by kinetic modeling, that enzymatic single-turnover (pre-steady-state) H-transfer reactions can be significantly complicated by kinetic isotope fractionation. This fractionation results in the formation of more protiated than deuterated product and is a unique problem for pre-steady-state reactions. When observed rate constants are measured using rapid-mixing (e.g., stopped flow) methodologies, kinetic isotope fractionation can lead to a large underestimation of both the magnitude and temperature dependence of kinetic isotope effects (KIEs). This fractionation is related to the isotopic purity of the substrates used and highlights a major problem with experimental studies which measure KIEs with substrates that are not isotopically pure. As it is not always possible to prepare isotopically pure substrates, we describe two general methods for the correction, for known isotope impurities, of KIEs calculated from pre-steady-state measurements. | 18,847,184 |
Lewis acid stabilized methylidene and oxoscandium complexes. | The methylidene scandium complex (PNP)Sc(mu3-CH2)(mu2-CH3)2[Al(CH3)2]2 (PNP = N[2-P(CHMe2)2-4-methylphenyl]2-) can be prepared from the reaction of (PNP)Sc(CH3)2 and 2 equiv of Al(CH3)3. The Lewis acid stabilized methylidenes candium complex has been crystallographically characterized, and its bonding scheme analyzed by DFT. In addition, we report preliminary reactivity studies of the Sc-CH2 ligand with substrates such as H2NAr and OCPh2. While the former results in an Brønsted acid-base reaction, the latter reagent produces the olefin H2C CPh2 along with the novel oxoscandium complex (PNP)Sc(mu3-O)(mu2-CH3)2[Al(CH3)2]2, quantitatively. | 18,847,190 |
Systematic synthesis, isolation, and photophysical properties of linear-shaped Re(I) oligomers and polymers with 2-20 units. | Systematic synthesis routes have been developed for the linear-shaped rhenium(I) oligomers and polymers bridged with bidentate phosphorus ligands, [Re(N--N)(CO)3-PP-{Re(N--N)(CO)2-PP-}(n)Re(N--N)(CO)3](PF6)(n+2) (N--N = diimine, PP = bidentate phosphine, n = 0-18). These were isolated by size exclusion chromatography (SEC) and identified by (1)H NMR, IR, electrospray ionization Fourier transform mass spectrometry, analytical SEC, and elemental analysis. Crystal structures of [Re(bpy)(CO)3-Ph2PC[triple bond]CPPh2-Re(bpy)(CO)3](PF6)2, [Re(bpy)(CO)3-Ph2PC[triple bond]CPPh2-Re(bpy)(CO)2-Ph2PC[triple bond]CPPh2-Re(bpy)(CO)3](PF6)3 and [Re(bpy)(CO)3-Ph2PC2H4PPh2-{Re(bpy)(CO)2Ph2PC2H4PPh2-}(n)Re(bpy)(CO)3](PF6)(n+2) (bpy = 2,2'-bipyridine, n = 1, 2) were obtained, showing that they have interligand pi-pi interaction between the bpy ligand and the phenyl groups on the phosphorus ligand. All of the oligomers and polymers synthesized were emissive at room temperature in solution. For the dimers, broad emission was observed with a maximum at 523-545 nm, from the (3)MLCT excited-state of the tricarbonyl complex unit, [Re(N--N)(CO)3-PP-]. Emission from the longer oligomers and polymers with > or = 3 Re(I) units was observed at wavelengths 50-60 nm longer than those of the corresponding dimers. This fact and the emission decay results clearly show that energy transfer from the edge unit to the interior unit occurs with a rate constant of (0.9 x 10(8))-(2.5 x 10(8)) s(-1). The efficient energy transfer and the smaller exclusive volume of the longer Re(I) polymers indicated intermolecular aggregation for these polymers in an MeCN solution. | 18,847,194 |
Ferromagnetic ordering in bisthiaselenazolyl radicals: variations on a tetragonal theme. | A series of five isostructural bisthiaselenazolyl radicals 2 have been prepared and characterized by X-ray crystallography. The crystal structures, all belonging to the tetragonal space group P42(1)m, consist of slipped pi-stack arrays of undimerized radicals packed about 4 centers running along the z-direction, an arrangement which gives rise to a complex lattice-wide network of close intermolecular Se---Se' contacts. Variations in R1 (Et, Pr, CH2CF3) with R2 = Cl lead to significant changes in the degree of slippage of the pi-stacks and hence the proximity of the Se---Se' interactions. By contrast, variations in R2 (Cl, Br, Me) with R1 = Et induce very little change in either the degree of slippage or the intermolecular contacts. Variable-temperature conductivity (sigma) measurements show relatively constant values for the conductivity sigma(300 K) (10(-5)-10(-4) S cm(-1)) and thermal activation energy E(act) (0.27-0.31 eV). Variable-temperature magnetic susceptibility measurements indicate that radicals 2b and 2c (R1 = Pr, CH2CF3; R2 = Cl) behave as weakly antiferromagnetically coupled Curie-Weiss paramagnets, but in 2a, 2d and 2e (R1 = Et; R2 = Cl, Me, Br) ferromagnetic ordering is observed, with T(c) values of 12.8 (R2 = Cl), 13.6 (R2 = Me), and 14.1 K (R2 = Br). The origin of the dramatically different magnetic behavior across the series has been explored in terms of a direct through-space mechanism by means of DFT calculations on individual pairwise exchange energies. These indicate that antiferromagnetic exchange between radicals along the pi-stacks increases with pi-stack slippage. | 18,847,197 |
Amine-functionalized task-specific ionic liquids: a mechanistic explanation for the dramatic increase in viscosity upon complexation with CO2 from molecular simulation. | The capture of CO2 from fossil fuel combustion, particularly in coal-fired power plants, represents a critical component of efforts aimed at stabilizing greenhouse gas levels in the atmosphere. Alkanolamines have traditionally been used to this end; however, drawbacks such as volatility, degradation, and regeneration costs have been drivers for the development of new, superior technologies. Recently, several seminal studies with ionic liquids (ILs), both experimental and computational, have demonstrated their potential as CO2 capture agents. In traditional ILs, experimental studies with CO2 have revealed its unusually high physical solubility in these media. Complementary simulation studies have provided evidence that this is attributable to CO2 occupying void space within the liquid and favorably interacting with the anion. Recently, a series of second-generation task-specific ionic liquids (TSILs) containing amine functional groups have been synthesized and demonstrated to have much higher capacities for CO2 due to their reactivity with CO2, as well unusually high viscosities in both the neat and complexed states. The current work extends the seminal studies of CO2 capture with ILs by providing insight from simulations into the mechanism responsible for the dramatic increase in viscosity upon complexation. Simulations conclusively demonstrate that the slow translational and rotational dynamics, which are manifest in the high viscosity, may be attributable to the formation of a strong, pervasive hydrogen-bonded network. Semiquantitative estimates of the cation and anion self-diffusion coefficients and rotational time constants, as well as detailed hydrogen bond analysis, are consistent with the experimentally observed formation of glassy or gel-like materials upon contact with CO2. This has significant implications for the design of new approaches or materials involving ILs that take advantage of these preconceived limitations, in the synthesis or manipulation of new TSIL frameworks for CO2 capture, and in novel experimental studies of chemistries and dynamics in persistent heterogeneous environments. | 18,847,198 |
Acoustic particle filter with adjustable effective pore size for automated sample preparation. | This article presents analysis and optimization of a microfluidic particle filter that uses acoustic radiation forces to remove particles larger than a selected size by adjusting the driving conditions of the piezoelectric transducer (PZT). Operationally, the acoustic filter concentrates microparticles to the center of the microchannel, minimizing undesirable particle adsorption to the microchannel walls. Finite element models predict the complex two-dimensional acoustic radiation force field perpendicular to the flow direction in microfluidic devices. We compare these results with experimental parametric studies including variations of the PZT driving frequencies and voltages as well as various particle sizes (0.5-5.0 microm in diameter). These results provide insight into the optimal operating conditions and show the efficacy of our device as a filter with an adjustable effective pore size. We demonstrate the separation of Saccharomyces cerevisiae from MS2 bacteriophage using our acoustic device. With optimized design of our microfluidic flow system, we achieved yields of greater than 90% for the MS2 with greater than 80% removal of the S. cerevisiae in this continuous-flow sample preparation device. | 18,847,218 |
A putative Fe2+-bound persulfenate intermediate in cysteine dioxygenase. | The common reactions of dioxygen, superoxide, and hydroperoxides with thiolates are thought to proceed via persulfenate intermediates, yet these have never been visualized. Here we report a 1.4 A resolution crystal structure of the Fe(2+)-dependent enzyme cysteine dioxygenase (CDO) containing this putative intermediate trapped in its active site pocket. The complex raises the possibility that, distinct from known dioxygenases and proposed CDO mechanisms, the Fe-proximal oxygen atom may be involved in the primary oxidation event yielding a unique three-membered Fe-S-O cyclic intermediate. A nonpolar environment of the distal oxygen would facilitate isomerization of the persulfenate to the sulfinate product. | 18,847,220 |
Quantitative evaluation of cross correlation between two finite-length time series with applications to single-molecule FRET. | The statistical properties of the cross correlation between two time series has been studied. An analytical expression for the cross correlation function's variance has been derived. On the basis of these results, a statistically robust method has been proposed to detect the existence and determine the direction of cross correlation between two time series. The proposed method has been characterized by computer simulations. Applications to single-molecule fluorescence spectroscopy are discussed. The results may also find immediate applications in fluorescence correlation spectroscopy (FCS) and its variants. | 18,847,232 |
On the structures of the diterpenes licamichauxiioic acids A and B. | The structures of the diterpenes licamichauxiioic acids A and B, isolated from Licania michauxii, which had been reported as 15-oxo-ent-kaur-9(11),16-dien-19-oic acid (1) and 15-oxo-ent-kaur-13,16-dien-19-oic acid (3), respectively, are not correct. Starting from grandiflorenic acid (6) we had prepared a compound with the proposed structure for licamichauxiioic acid A, and its spectroscopic data are different from those given for this acid. In the case of licamichauxiioic acid B, its NMR data are not in accordance with the proposed structure 3, which also violates Bredt's rule. In addition, we described a useful method for the separation of grandiflorenic and grandiflorolic acids. | 18,847,245 |
Trans-selective asymmetric aziridination of diazoacetamides and N-Boc imines catalyzed by axially chiral dicarboxylic acid. | Axially chiral dicarboxylic acid (R)-1d catalyzed reaction of diazoacetamides and N-Boc imines provided a novel organocatalytic means for the formation of enantiomerically enriched N-Boc protected trans aziridines. | 18,847,267 |
Tyrosine derivatives isolated from Streptomyces sp. IFM 10937 in a screening program for TRAIL-resistance-overcoming activity. | Exploration of actinomycetes for isolation of natural products for abrogating TRAIL resistance led to the isolation of two new tyrosine derivatives (1 and 2) along with novobiocin (3). The structures of 1 and 2 were determined by spectroscopic methods, while the absolute configuration was determined by analyzing CD spectra and by a modified Marfey's method. Compounds 1 (150 μM) and 3 (37.5 and 75 μM) in combination with TRAIL showed synergistic activity in sensitizing TRAIL-resistant human gastric adenocarcinoma cells. | 18,847,278 |
Measuring an antibody affinity distribution molecule by molecule. | Single molecule fluorescence microscopy was used to observe the binding and unbinding of hapten decorated quantum dots to individual surface immobilized antibodies. The fluorescence time history from an individual antibody site can be used to calculate its binding affinity. While quantum dot blinking occurs during these measurements, we describe a simple empirical method to correct the apparent/observed affinity to account for the blinking contribution. The combination of many single molecule affinity measurements from different antibodies yields not only the average affinity, it directly measures the full shape and character of the surface affinity distribution function. | 18,847,284 |
Electroporation of skeletal muscle induces danger signal release and antigen-presenting cell recruitment independently of DNA vaccine administration. | Plasmid DNA vaccination combined with electroporation (EP) provides a promising approach for the prevention of infectious diseases and for cancer immunotherapy. This technology has been described as being effective in activating humoral and cellular immune response in the host as well as in enhancing expression of the encoded antigen. Several reports showed EP has adjuvant-like properties when combined with plasmid DNA injection although the effect in the absence of DNA has not been investigated. The aim of this study is to clarify whether the application of EP alone to the skeletal muscle is able to recruit and trigger cells involved in antigen presentation and immune response. Mouse skeletal muscle treated by EP were observed and processed for clinical, histological and immunohistochemistry analysis at different time points. We demonstrate that EP induces transient morphological changes in the muscle with early production of endogenous cytokines responsible for signalling danger at the local level. Moreover, it causes the recruitment of inflammatory cells independently of the DNA injection and the activation of a danger pro-inflammatory pathway, resulting in T-lymphocyte migration. Our data indicate EP by itself is able to recruit and trigger cells involved in antigen presentation and immune response; hence, the idea that EP has adjuvant-like properties owing to a moderate tissue injury and generation of a pro-inflammatory context with cytokine release that enhances the immune response. We suggest EP may be of practical use in clinical protocols, contributing to the development of DNA vaccination strategies. | 18,847,301 |
Natural Treg in autoimmune diabetes: all present and correct? | The critical role for regulatory T cells (Treg) in suppressing autoimmune pathology is now well recognised. However, the extent to which defects in regulation can be blamed for the onset of diseases like type 1 diabetes is not clear. To collate the available data from mouse models and from studies of type 1 diabetes patients, with a view to understanding the status of the natural Treg compartment in this disease setting. Available evidence suggests that natural Treg are not under-represented in type 1 diabetes, and that Treg function is only likely to be suboptimal in a subset of patients. Emerging therapeutic strategies that attempt to exploit our knowledge of Treg biology to restore effective immune regulation in type I diabetes are discussed. | 18,847,305 |
The evolution of biomarkers in rheumatoid arthritis: from clinical research to clinical care. | Treatment efficacy in rheumatoid arthritis (RA) has been measured by clinical response, gross radiological results and some biochemical markers. With the new biologic treatments, markers for disease development, progress, severity and therapy response have evolved. This review focuses on a selection of current markers and the need for better markers for determining RA treatment susceptibility and success. A review of the literature was conducted and expert opinions expressed. Current biomarkers mainly focus on disease activity and severity. Biomarkers for treatment response and susceptibility that help clinicians make initial treatment decisions are lacking or insufficient, yet required for optimal control of RA. A combination of biomarkers is necessary to classify a complex immune disease, such as RA. | 18,847,311 |
Sialome individuality between Aedes aegypti colonies. | Aedes aegypti is responsible for the transmission of arboviruses. The Yellow Fever, Dengue and Chikungunya viruses are transmitted to the vertebrate host by injection of infected saliva during the blood meal of its vectors. Saliva contains different components with various biochemical activities; anti-hemostatic, angiogenic, inflammatory, and immunomodulatory. This work compares the sialomes of three Ae. aegypti colonies (Rockefeller, PAEA, and Formosus), where the repertoire of salivary proteins from these colonies was analyzed by a proteomic approach. This study indicated that major proteins were detectable in the three colonies. However, differences in the abundance of some saliva proteins have been observed between the three Ae. aegypti colonies. | 18,847,318 |
Combination treatment with a selective androgen receptor modulator q(SARM) and a bisphosphonate has additive effects in osteopenic female rats. | Recent clinical trials with bisphosphonates and PTH have not supported the hypothesis that combination treatments with antiresorptive and anabolic agents would lead to synergistic activity. We hypothesized that combination treatment with a selective androgen receptor modulator (SARM), LGD-3303, and a bisphosphonate would be beneficial. In vitro competitive binding and transcriptional activity assays were used to characterize LGD-3303. LGD-3303 is a potent nonsteroidal androgen that shows little or no cross-reactivity with related nuclear receptors. Tissue selective activity of LGD-3303 was assessed in orchidectomized male rats orally administered LGD-3303 for 14 days. LGD-3303 increased the levator ani muscle weight above eugonadal levels but had greatly reduced activity on the prostate, never increasing the ventral prostate weight to >50% of eugonadal levels even at high doses. Ovariectomized female rats were treated with LGD-3303, alendronate, or combination treatment to study the effects on bone. DXA scans, histomorphometry, and biomechanics were performed. LGD-3303 increased muscle weight in females rats. In addition, LGD-3303 increased BMD and BMC at both cortical and cancellous bone sites. At cortical sites, the effects were caused in part by anabolic activity on the periosteal surface. At every measured site, combination treatment was as effective as either single agent and in some cases showed significant added benefit. LGD-3303 is a novel SARM with anabolic effects on muscle and cortical bone not observed with bisphosphonates. Combination therapy with LGD-3303 and alendronate had additive effects and may potentially be a useful therapy for osteoporosis and frailty. | 18,847,323 |
Nanofabricated collagen-inspired synthetic elastomers for primary rat hepatocyte culture. | Synthetic substrates that mimic the properties of extracellular matrix proteins hold significant promise for use in systems designed for tissue engineering applications. In this report, we designed a synthetic polymeric substrate that is intended to mimic chemical, mechanical, and topological characteristics of collagen. We found that elastomeric poly(ester amide) substrates modified with replica-molded nanotopographic features enhanced initial attachment, spreading, and adhesion of primary rat hepatocytes. Further, hepatocytes cultured on nanotopographic substrates also demonstrated reduced albumin secretion and urea synthesis, which is indicative of strongly adherent hepatocytes. These results suggest that these engineered substrates can function as synthetic collagen analogs for in vitro cell culture. | 18,847,357 |
Introduction of a novel prototype bioartificial liver support system utilizing small human hepatocytes in rotary culture. | The aim of this study was to establish a stand-alone, perfused, rotary cell culture system using small human hepatocytes (SH) for bioartificial liver (BAL) support. SH were grown on cytodex 3 microcarriers (beads) to a maximum density of 1.2 +/- 0.3 x 10(7) cells per mL within 12 days. Size of aggregates formed by up to 15 beads was regulated by rotation speed. Cell function was proven by treatment with ammonia and galactose, and metabolism was analyzed. Treatment strategy was comprised of two phases, namely growth phase and treatment phase. Cells were grown for 6 days and subsequently incubated with ammonia or galactose for 2 days, followed by a 2-day regeneration period and another 2-day treatment phase. Consumption of glucose, release of lactate dehydrogenase, formation of lactate, and production of urea and albumin were determined regularly. Mean galactose consumption was 50 microg per 106 cells per hour, ammonia-induced urea formation was 3.6 microg per 106 cells per hour, and albumin production was 110 ng per 106 cells per hour. All metabolic parameters followed a logarithmic trend and were found to be very stable in the second half of the culture period when cells were treated with ammonia or galactose. Dissolved oxygen (%DO), pH, and temperature were monitored in-stream at intervals of 7 min, and the values were logged. Viability and morphology of cells were monitored via confocal microscopy. Viability was around 95% in controls and 90% during treatment. Promising results were obtained in support of our ongoing efforts to establish a fully autonomous BAL support device utilizing SH as a bridge to transplantation. | 18,847,359 |
Oxidative stress, free radicals and bone remodeling. | Reactive oxygen species (ROS) are widely considered to be a causal factor in aging and in a number of pathological conditions, such as atherosclerosis, carcinogenesis and infarction. Their role in bone metabolism is dual, considering their effects under physiological or pathological conditions. Under physiological conditions, the production of ROS by osteoclasts helps accelerate destruction of calcified tissue, thus assisting in bone remodeling. In pathological conditions, when a bone fractures, e.g., radical generation is remarkably high. However, though the increases in osteoclastic activity and ROS production are linked in many skeletal pathologies, it remains to be clarified whether increased ROS production overwhelms antioxidant defenses, leaving the individual open to hyperoxidant stress. | 18,847,368 |
Antimicrobial susceptibility of foodborne pathogens in organic or natural production systems: an overview. | Organic and natural food production systems are increasing in popularity, at least partially because consumers perceive that these niche markets provide healthier and safer food products. One major difference between these niche markets and conventional production systems is the use of antimicrobials. Because antimicrobial agents exert selective pressures for antimicrobial resistance, relating antimicrobial susceptibility of foodborne bacteria to niche market production systems is of interest. Other differences between production systems might also influence the susceptibility of foodborne pathogens. The objective of this review is to compare the impact of food animal production systems on the antimicrobial susceptibility of common foodborne bacterial pathogens. Studies comparing the susceptibility of such pathogens were diverse in terms of geographic location, procedures, species of bacteria, and antimicrobials evaluated; thus, it was difficult to draw conclusions. The literature is highly variable in terms of production type and practices and susceptibility associations, although few studies have compared truly organic and conventional practices. When statistical associations were found between production type and minimum inhibitory concentrations or percentage of isolates resistant for a particular pathogen, the isolates from conventionally reared animals/products were more commonly resistant than the comparison group (organic, antibiotic free, etc.). Therefore, further studies are needed to better assess public health consequences of antimicrobial resistance and food animal production systems, specifically organic or natural versus conventional. | 18,847,380 |
Expressions of HIV-related stigma among rural-to-urban migrants in China. | In China, HIV-related stigma is considered as a formidable barrier in the combat against the HIV epidemic. There have been few qualitative investigations on HIV-related stigma in China, especially among a vulnerable population of rural-to-urban migrants. Based on 90 in-depth interviews conducted in 2002-2003 with rural-to-urban migrants in Beijing and Nanjing, China, this study examines the forms and expressions of HIV-related stigma from migrants' perspectives regarding HIV infection and individuals at risk of HIV infection. Consistent with the general framework on stigma, Chinese rural-to-urban migrants' attitudes toward HIV infected individuals take forms of denial, indifference, labeling, separation, rejection, status loss, shame, hopelessness, and fear. These stigmatizing attitudes were mainly derived from fears of AIDS contagion and its negative consequences, fears of being associated with the diseases, and culturally relevant moral judgments. In addition to universal AIDS stigma, both traditional Chinese culture and socially marginalized position of rural migrant population have contributed to culturally unique aspects of stigmatizing attitudes among rural-to-urban migrants. These multifaceted manifestations of HIV-related stigma suggest that HIV stigma reduction intervention needs to address multiple aspects of HIV stigma and stigmatization including personal, cultural, institutional, and structural factors. | 18,847,389 |
Resistance in bacteria of the food chain: epidemiology and control strategies. | Bacteria have evolved multiple mechanisms for the efficient evolution and spread of antimicrobial resistance. Modern food production facilitates the emergence and spread of resistance through the intensive use of antimicrobial agents and international trade of both animals and food products. The main route of transmission between food animals and humans is via food products, although other modes of transmission, such as direct contact and through the environment, also occur. Resistance can spread as resistant pathogens or via transferable genes in different commensal bacteria, making quantification of the transmission difficult. The exposure of humans to antimicrobial resistance from food animals can be controlled by either limiting the selective pressure from antimicrobial usage or by limiting the spread of the bacteria/genes. A number of control options are reviewed, including drug licensing, removing financial incentives, banning or restricting the use of certain drugs, altering prescribers behavior, improving animal health, improving hygiene and implementing microbial criteria for certain types of resistant pathogens for use in the control of trade of both food animals and food. | 18,847,409 |
Aberrant promoter CpG island hypermethylation of the adenomatosis polyposis coli gene can serve as a good prognostic factor by affecting lymph node metastasis in squamous cell carcinoma of the esophagus. | There has been no clear evidence demonstrating whether DNA hypermethylation can affect the prognosis of esophageal cancer. We collected tissue from 50 cases of squamous cell carcinoma of the esophagus and tested them for DNA hypermethylation using methylation-specific polymerase chain reaction. CpG island hypermethylations were observed in 10% for p16, 34% for RARbetaP2, 46% for adenomatosis polyposis coli (APC), 14% for RASSF1A, 84% for FHIT, and 8% for hMLH1. APC promoter hypermethylation was frequently found in patients without lymph node metastasis compared with those with lymph node metastasis (62.5% : 30.8%, P = 0.025). The number of metastatic lymph nodes were lower in patients with APC promoter hypermethylation (0.87 +/- 0.30 : 3.07 +/- 0.72, P = 0.008). Excluding operative mortalities and incomplete resections, 42 patients were analyzed for long-term outcome. During the mean follow-up period of 35 months, 17 developed recurrence and 14 died of cancer. Ten patients died of other causes. In univariable analysis, unmethylation of APC (P = 0.0015) and FHIT (P = 0.0044), as well as presence of lymph node metastasis (P = 0.0038), were risk factors for recurrence. In multivariable analysis, lymph nodes metastasis (P = 0.050) and unmethylation of APC promoter (P = 0.023) remained as significant risk factors. In conclusion, promoter hypermethylation of the APC gene is related to a lower number of metastatic lymph nodes and to superior prognosis in terms of recurrence, which suggests it might be involved in the process of lymph node metastasis in esophageal cancer. | 18,847,451 |
Can immune-enhancing nutrients reduce postoperative complications in patients undergoing esophageal surgery? | Postoperative infection of esophageal neoplasm surgery is the major cause of prolonged postoperative hospitalization, as well as morbidity. The clinical benefits of administering immune-enhancing nutrients (IEN) to critically ill patients and those undergoing elective surgery were clarified. However, the benefits of preoperative administration of IEN for patients with esophageal cancer remain unclear. The present study was designed to clarify the clinical efficacy of administration of IEN prior to esophageal surgery. A total of 123 patients undergoing esophagectomy in single institute were retrospectively investigated. All patients received postoperative enteral nutrition by use of ordinal nutrients. Preoperative IEN were also given to 84 patients (IEN group), while the other 39 received an ordinary diet (control). Postoperative courses and laboratory data were compared between the two groups. The incidences of infectious complications in the IEN and control groups were 18% and 38%, respectively (P < 0.05). Pneumonia developed in 5 (6%) IEN and 7 (18%) control patients (P < 0.05). Postoperative hospitalization was shorter in the IEN group (P < 0.01). Prealbumin levels, retinal binding protein levels and the lymphocyte count were significantly higher in the IEN group on postoperative day 3. These results suggest that preoperative administration of IEN in patients undergoing esophagectomy reduces infectious complications, mainly pneumonia, and shortens postoperative hospitalization. | 18,847,452 |
Genomics research: world survey of public funding. | Over the past two decades, genomics has evolved as a scientific research discipline. Genomics research was fueled initially by government and nonprofit funding sources, later augmented by private research and development (R&D) funding. Citizens and taxpayers of many countries have funded much of the research, and have expectations about access to the resulting information and knowledge. While access to knowledge gained from all publicly funded research is desired, access is especially important for fields that have broad social impact and stimulate public dialogue. Genomics is one such field, where public concerns are raised for reasons such as health care and insurance implications, as well as personal and ancestral identification. Thus, genomics has grown rapidly as a field, and attracts considerable interest. One way to study the growth of a field of research is to examine its funding. This study focuses on public funding of genomics research, identifying and collecting data from major government and nonprofit organizations around the world, and updating previous estimates of world genomics research funding, including information about geographical origins. We initially identified 89 publicly funded organizations; we requested information about each organization's funding of genomics research. Of these organizations, 48 responded and 34 reported genomics research expenditures (of those that responded but did not supply information, some did not fund such research, others could not quantify it). The figures reported here include all the largest funders and we estimate that we have accounted for most of the genomics research funding from government and nonprofit sources. Aggregate spending on genomics research from 34 funding sources averaged around $2.9 billion in 2003-2006. The United States spent more than any other country on genomics research, corresponding to 35% of the overall worldwide public funding (compared to 49% US share of public health research funding for all purposes). When adjusted to genomics funding intensity, however, the United States dropped below Ireland, the United Kingdom, and Canada, as measured both by genomics research expenditure per capita and per Gross Domestic Product. | 18,847,466 |
PCR and real-time PCR primers developed for detection and identification of Bifidobacterium thermophilum in faeces. | Culture-independent methods based on the 16S ribosomal RNA molecule are nowadays widely used for assessment of the composition of the intestinal microbiota, in relation to host health or probiotic efficacy. Because Bifidobacterium thermophilum was only recently isolated from human faeces until now, no specific real-time PCR (qPCR) assay has been developed for detection of this species as component of the bifidobacterial community of the human intestinal flora. Design of specific primers and probe was achieved based on comparison of 108 published bifidobacterial 16S rDNA sequences with the recently published sequence of the human faecal isolate B. thermophilum RBL67. Specificity of the primer was tested in silico by similarity search against the sequence database and confirmed experimentally by PCR amplification on 17 Bifidobacterium strains, representing 12 different species, and two Lactobacillus strains. The qPCR assay developed was linear for B. thermophilum RBL67 DNA quantities ranging from 0.02 ng/microl to 200 ng/microl and showed a detection limit of 10(5) cells per gram faeces. The application of this new qPCR assay allowed to detect the presence of B. thermophilum in one sample from a 6-month old breast-fed baby among 17 human faecal samples tested. Additionally, the specific qPCR primers in combination with selective plating experiments led to the isolation of F9K9, a faecal isolate from a 4-month old breast-fed baby. The 16S rDNA sequence of this isolate is 99.93% similar to that of B. thermophilum RBL67 and confirmed the applicability of the new qPCR assay in faecal samples. A new B. thermophilum-specific qPCR assay was developed based on species-specific target nucleotides in the 16S rDNA. It can be used to further characterize the composition of the bifidobacterial community in the human gastrointestinal tract. Until recently, B. thermophilum was considered as a species of animal origin, but here we confirm with the application of this new PCR assay the presence of B. thermophilum strains in the human gut. | 18,847,469 |
Molecular and phylogenetic analysis of HIV-1 variants circulating in Italy. | The continuous identification of HIV-1 non-B subtypes and recombinant forms in Italy indicates the need of constant molecular epidemiology survey of genetic forms circulating and transmitted in the resident population. The distribution of HIV-1 subtypes has been evaluated in 25 seropositive individuals residing in Italy, most of whom were infected through a sexual route during the 1995-2005 period. Each sample has been characterized by detailed molecular and phylogenetic analyses. 18 of the 25 samples were positive at HIV-1 PCR amplification. Three samples showed a nucleotide divergence compatible with a non-B subtype classification. The phylogenetic analysis, performed on both HIV-1 env and gag regions, confirms the molecular sub-typing prediction, given that 1 sample falls into the C subtype and 2 into the G subtype. The B subtype isolates show high levels of intra-subtype nucleotide divergence, compatible with a long-lasting epidemic and a progressive HIV-1 molecular diversification. The Italian HIV-1 epidemic is still mostly attributable to the B subtype, regardless the transmission route, which shows an increasing nucleotide heterogeneity. Heterosexual transmission and the interracial blending, however, are slowly introducing novel HIV-1 subtypes. Therefore, a molecular monitoring is needed to follow the constant evolution of the HIV-1 epidemic. | 18,847,472 |
Functional identification of NR2 subunits contributing to NMDA receptors on substance P receptor-expressing dorsal horn neurons. | NMDA receptors are important elements in pain signaling in the spinal cord dorsal horn. They are heterotetramers typically composed of two NR1 and two of four NR2 subunits: NR2A-2D. Mice lacking specific NR2 subunits show deficits in pain transmission yet subunit location in the spinal cord remains unclear. We have combined electrophysiological and pharmacological approaches to investigate the composition of functional NMDA receptors expressed by lamina I, substance P receptor-expressing (NK1R+) neurons, as well as NK1R- neurons. Under low Mg2+ conditions (100 microM), the conductance of NMDA receptors at -90 mV (g(-90 mV)) with NR2A or NR2B subunits (NR2A/B) is low compared to conductance measured at the membrane potential where the inward current is maximal or maximal inward current (MIC) (ratio of approximately 0.07 calculated from Kuner and Schoepfer, 1996). For NR2C or NR2D subunits (NR2C/D), the ratio is higher (ratio approximately 0.4). NK1R+ and NK1R- neurons express NMDA receptors that give ratios approximately 0.28 and 0.16, respectively, suggesting both types of subunits are present in both populations of neurons, with NK1R+ neurons expressing a higher percentage of NR2C/D type NMDA receptors. This was confirmed using EAB318, an NR2A/B preferring antagonist, and UBP141, a mildly selective NR2C/D antagonist to increase and decrease the g(-90 mV)/g(MIC) ratios in both subpopulations of neurons. | 18,847,474 |
Cadaveric and three-dimensional computed tomography study of the morphology of the scapula with reference to reversed shoulder prosthesis. | The purpose of this study is to analyze the morphology of the scapula with reference to the glenoid component implantation in reversed shoulder prosthesis, in order to improve primary fixation of the component. Seventy-three 3-dimensional computed tomography of the scapula and 108 scapular dry specimens were analyzed to determine the anterior and posterior length of the glenoid neck, the angle between the glenoid surface and the upper posterior column of the scapula and the angle between the major craneo-caudal glenoid axis and the base of the coracoid process and the upper posterior column. The anterior and posterior length of glenoid neck was classified into two groups named "short-neck" and "long-neck" with significant differences between them. The angle between the glenoid surface and the upper posterior column of the scapula was also classified into two different types: type I (mean 50 degrees-52 degrees ) and type II (mean 62.50 degrees-64 degrees ), with significant differences between them (p < 0.001). The angle between the major craneo-caudal glenoid axis and the base of the coracoid process averaged 18,25 degrees while the angle with the upper posterior column of the scapula averaged 8 degrees . Scapular morphological variability advices for individual adjustments of glenoid component implantation in reversed total shoulder prosthesis. Three-dimensional computed tomography of the scapula constitutes an important tool when planning reversed prostheses implantation. | 18,847,487 |
Session 2: Personalised nutrition. Metabolomic applications in nutritional research. | Metabolomics aims to profile all small molecules that are present in biological samples such as biofluids, tissue extracts and culture media. Combining the data obtained with multivariate data analysis tools allows the exploration of changes induced by a biological treatment or changes resulting from phenotype. Recently, there has been a large increase in interest in using metabolomics in nutritional research and because of the intimate relationship between nutrients and metabolism there exists great potential for the use of metabolomics within nutritional research. However, for metabolomics to reach its full potential within this field it is also important to be realistic about the challenges that are faced. Examples of such challenges include the necessity to have a clear understanding of the causes of variation in human metabolomic profiles, the effects of the gut microflora on the metabolomic profile and the interaction of the gut microflora with the host's metabolism. A further challenge that is particularly relevant for human nutritional research is the difficulty associated with biological interpretation of the data. Notwithstanding these and other challenges, several examples of successful applications to nutritional research exist. The link between the human metabolic phenotype, as characterised by metabolomic profiles, and dietary preferences proposes the potential role of metabolomics in personalised nutrition. | 18,847,517 |
Etiological factors and mortality of acute intestinal obstruction: a review of 705 cases. | To figure out the etiological factors and overall mortality of the patients with acute intestinal obstruction, and to explore the rational period of conservative therapy before operation. Medical records of all the patients with acute intestinal obstruction admitted to West China Hospital from 1995 to 2002 were retrospectively reviewed. The etiology of the obstruction was categorized, and the correlation of mortality and time interval between conservative therapy and operation was analyzed. There were 705 patients with acute intestinal obstruction included. There were 71.1% of the obstruction lesions located on the small bowel, and 82.6% of the patients experienced simple obstruction. The most frequent cause was adhesions (62.0%), and next was neoplasms (23.7%). There were 57.6% of the patients underwent the surgical treatment. The overall mortality rate was 1.6%, and the mortality rates in conservative therapy and surgical intervention groups were 1.3% and 1.7% respectively. The intestinal necrosis rate was increased gradually with the prolongation of time interval between conservative therapy and operation, and the death might occur 24 hours after strangulation. The epidemiological transition to adhesive obstruction still exists in China, and it is similar to that in Western countries. In our experience, near half of the patients with simple obstruction may achieve palliation by conservative therapy. Surgical intervention is indicated for the patients with prolonged and non-palliated simple obstruction, or strangulation disease within the first 24 hours. | 18,847,534 |
[Illicit drugs, medications and traffic accidents]. | The European Union (EU) has 25 member-states and 455 million inhabitants. Statistics on traffic accidents in the EU show that more than 45,000 people are killed annually, including 5200 in France. At the same time, nearly two million persons in the EU require medical treatment for traffic-accident-related injuries, including 109,000 in France. In addition, traffic accidents are the major cause of death of those individuals aged 15 to 24 years. One third of the EU inhabitants will be hospitalized during their life due to a traffic accident with a cost over 160 billion euro (2-3% of the Gross Domestic Product). An important contributing factor to crashes is the use of alcohol and/or illicit drugs or medication when driving, as they exert negative effects on cognition and psychomotor functions. For illicit drugs, abuse of cannabis with or without alcohol is a major concern for the EU. In fact, three million Europeans use cannabis daily and 80% of them drive after use. A number of French studies since 1999 have underlined the high prevalence of cannabis found in the blood of injured or killed drivers. From medical or judicial observations, it is clear that cannabis use increases the risk of traffic accidents. Many groups outside Europe have also shown the association between drug abuse and crashes. The number of casualties related to certain medicines, especially benzodiazepines remains at a high level, particularly in the elderly. In many countries the prevalence of medicinal drugs associated with car accidents is higher than with cannabis. Annex III of the European Union Council Directive of July the 29th 1991 in fact states that a driving license should not be issued to or renewed for applicants or drivers who are dependent on psychotropic substances or use them regularly. Recently, France has categorized the medicinal drugs available in the country by using three pictograms: level one yellow, "be careful"; level two orange, "be very careful"; level three red, "don't drive". It is an important campaign that increases awareness among the public and the medical professionals about the potential dangerous effects of medicinal drugs when driving. The EU objective of reducing the number of fatalities to 25,000 by 2010 will require strengthening measures against the use of alcohol, illicit and medicinal drugs by not well-informed drivers. It is not only a really great challenge, but also a significant investment towards improving public health in France as well as in Europe. | 18,847,565 |
[Similarity of biotechnology-derived drugs: regulatory framework and specificity]. | Directive 2004/27/EC, issued by the European commission specifies the conditions by which marketing approval can be awarded for a biosimilar drug, whose structure is the closest possible to that of an already marketed biotechnology-drug. This specific regulation differs in more than one point from that applied to classical generic products. Others conditions beyond the sole demonstration of in vivo bioequivalence should be satisfied to ensure prudent, i.e., without risk to the patient, therapeutic substitution. | 18,847,566 |
[Cannabis and safety of work. Evolution of its detection within the controls of narcotics since 2004 to the SNCF]. | Fifteen to 20 % of fatal work-related accidents would be connected to the use of alcohol, psychotrops or narcotics. Many constraints restrain the systematic detection of addictive behaviour at work. The restraints can be financial, ethical, technical or laid down in the regulations. The occupational physician remains the main actor in the prevention of the risks caused by those behaviours. In 2004, the firm SNCF engaged a long-term action of drugs information and detection. It has been well-understood by the agents and all the firm's operators achieved in appropriated conditions, with a strict respect of the medical secret. In four years, the number of detected consumers decreased by half. | 18,847,573 |
A prospective evaluation of the effect of sample collection site on intraoperative parathormone monitoring during parathyroidectomy. | Sample collection site may affect the dynamics of intraoperative parathyroid hormone monitoring (IPM) and influence surgical decisions. We prospectively studied 45 patients undergoing parathyroidectomy for primary hyperparathyroidism. The IPM cure criterion was a decrease in peripheral vein (PV) parathyroid hormone (PTH) of >50% at 10 minutes after gland excision. PTH samples were collected simultaneously from PV and central vein (CV) and compared for PTH decay, the incidence of >50% PTH decay, and the incidence of normal PTH values after gland excision. Mean PTH levels were significantly higher from the CV before and after gland excision. Mean PTH decay 10 minutes after gland excision was 89% PV versus 88% CV, resulting in mean PTH levels of 27 +/- 23 and 39 +/- 35 pg/mL, respectively (P < .0001). At 5 minutes, >50% decay in PTH was present in 98% PV versus 88% CV samples. By 10 minutes, the incidence of >50% PTH decay was equivalent (98%). This yielded normal range PTH levels from the PV versus CV in 90% versus 76% of patients at 5 minutes, 96% versus 89% at 10 minutes, and 95% versus 81% at 20 minutes. Of 45 patients, 44 (98%) are normocalcemic at a mean follow-up of 6.3 months. IPM predicted the single operative failure. CV sampling produces significantly higher PTH levels. Surgeons sampling from a PV may observe a >50% decrease in PTH and normal range PTH values starting 5 minutes after gland excision. Surgeons who sample from the CV and require normalization of PTH levels may have to wait longer and/or continue potentially unnecessary neck exploration. | 18,847,632 |
Human error, not communication and systems, underlies surgical complications. | This study prospectively assesses the underlying errors contributing to surgical complications over a 12-month period in a complex academic department of surgery using a validated scoring template. Studies in "high reliability organizations" suggest that systems failures are responsible for errors. Reports from the aviation industry target communication failures in the cockpit. No prior studies have developed a validated classification system and have determined the types of errors responsible for surgical complications. A classification system of medical error during operation was created, validated, and data collected on the frequency, type, and severity of medical errors in 9,830 surgical procedures. Statistical analysis of concordance, validity, and reliability were performed. Reported major complications occurred in 332 patients (3.4%) with error in 78.3%: errors in surgical technique (63.5%), judgment errors (29.6%), inattention to detail (29.3%), and incomplete understanding (22.7%). Error contributed more than 50% to the complication in 75%. A total of 13.6% of cases had error but no injury, 34.4% prolongation of hospitalization, 25.1% temporary disability, 8.4% permanent disability, and 16.0% death. In 20%, the error was a "mistake" (the wrong thing), and in 58% a "slip" (the right thing incorrectly). System errors (2%) and communication errors (2%) were infrequently identified. After surgical technique, most surgical error was caused by human factors: judgment, inattention to detail, and incomplete understanding, and not to organizational/system errors or breaks in communication. Training efforts to minimize error and enhance patient safety must address human factor causes of error. | 18,847,639 |
Reoperative parathyroidectomy: an algorithm for imaging and monitoring of intraoperative parathyroid hormone levels that results in a successful focused approach. | Advances in preoperative imaging and use of intraoperative parathyroid hormone (IOPTH) levels are changing the approach to reoperative parathyroidectomy (ReopPTX). We sought to develop a protocol for imaging and IOPTH monitoring that allows for a focused, successful operative approach. We reviewed our prospective database of consecutive patients with primary hyperparathyroidism who underwent ReopPTX with IOPTH monitoring between December 1999 and June 2007. Thirty-nine patients underwent 43 ReopPTXs for persistent (79%)/recurrent (21%) disease. All underwent ultrasonography and sestamibi imaging; 24 cases (56%) underwent additional imaging studies. Sensitivity of ultrasonography was 56%, sestamibi 53%, both studies 67%, computed tomography (CT) 48%, magnetic resonance imaging (MRI) 67%, and selective venous sampling (SVS) 50%. IOPTH monitoring predicted accurately cure in 100% and failure in 78%. A focused/unilateral approach was performed in 60%; median operative time was 45 minutes (range, 12-127). At last follow-up, 36 (92%) patients were normocalcemic. We propose that ultrasonography and sestamibi studies should be done before all ReopPTXs; failure to localize should prompt sequential CT, MRI, and SVS until localization is achieved. IOPTH monitoring defines cure and is recommended for all ReopPTXs. This algorithm allows for a focused operative approach in >50% of ReopPTXs with operative times comparable with first-time, minimally invasive parathyroidectomy. | 18,847,646 |
Algorithm for head computed tomography imaging in patients with mandible fractures. | Trauma to the mandible can potentially increase our predictive accuracy for intracranial injuries (ICIs) because of the mandible's strength, anatomic proximity, and direct connection to the skull base. Our goals were to: 1) investigate the association of mandible fractures with traumatic brain injury (TBI) and intracranial lesions (ICLs); and 2) determine predictors of ICIs in a level 1 Canadian trauma center with distinct patient demographics and fracture etiologies. A retrospective chart review was performed of medical records of mandible-fracture patients treated at our institution from 1997 to 2003. Patients who had undergone postinjury computed tomography (CT) of the head with a minimum of 4 weeks' follow-up were considered eligible. Data collected included patient and fracture characteristics, neurologic evaluation, and the presence of concomitant injuries. One hundred eighty-one patients were reviewed, of whom 86 were found eligible, with demographics representative of an urban-trauma population. The incidence of TBI was 68.6%, and of ICLs, 27%. Logistic regression identified alcohol (odds ratio [OR], 3.97), concomitant facial fracture (OR, 2.77), and other systemic injury (OR, 2.59) as independent predictors of an ICI in mandibular fracture patients. Importantly, ICIs were observed in 19% of mandible-fracture patients, satisfying the criteria for mild TBI, and in 17% of patients without any evidence of TBI. Some authors have advocated treating mandible fractures on an outpatient basis, with a focused workup. Our results of significant concomitant ICI in mandible-fracture patients, conversely, suggest that such management may inadvertently result in the oversight of potentially life-threatening injuries. Thus, we recommend mandatory intracranial CT imaging if the patient's neurologic status at time of injury is unknown or meets the criteria of TBI, or if positive predictors for ICL are present. | 18,848,107 |
Secondarily stabilized dental implants: an alternative to sinus grafting--early clinical results of 63 consecutively placed implants. | A standard dental implant modified with an apical cross-screw was studied clinically in the posterior maxilla in a trial of 63 sinus-penetrating implants. Twenty-five patients who had cross-screw implants placed in the atrophic posterior maxilla were followed for up to 3 years. Of 63 implants placed, 5 implants failed over a 4-year study period for a 92.1% success rate. Despite the implant body penetrating into the sinus cavity, no long-term complication resulted. Threaded dental implants that were stabilized secondarily with a cross-screw maintained stability and did not disturb sinus cavity health over a 3-year period. | 18,848,114 |
Long-term impact of drug-eluting stents versus bare-metal stents on all-cause mortality. | Our purpose was to examine the incidence of all-cause mortality among drug-eluting stents (DES) and bare-metal stents (BMS) while adjusting for many confounding factors generally not considered in prior studies. DES use in the U.S. declined by up to 50% in recent years, primarily due to concerns about late stent thrombosis and possibly increased mortality. However, recent data suggest that DES are as safe as BMS and may actually be associated with a lower incidence of myocardial infarction and mortality. All patients undergoing percutaneous coronary intervention with a DES or BMS alone from March 1, 2003, to June 30, 2007, at a tertiary care center were assessed. Multivariable Cox proportional hazards modeling was performed for overall and propensity-matched patients. Socioeconomic status was calculated using U.S. Census 2000 data. The primary end point was all-cause mortality. There were a total of 832 deaths over a 4.5-year interval among 8,032 patients. Of these, 6,053 received a DES and 1,983 patients had a BMS. All-cause mortality was significantly lower in unadjusted and adjusted Cox proportional models with DES (hazard ratio: 0.62, 95% confidence interval: 0.53 to 0.73; p < 0.001). Similarly, in the propensity-matched group, DES remained associated with lower mortality compared with BMS (adjusted hazard ratio: 0.54, 95% confidence interval: 0.45 to 0.66; p < 0.001). DES were associated with lower mortality in this "real-world" setting. However, despite multiple adjustments, potential confounding may still play a role. | 18,848,135 |
Venous thromboembolism in Spain. Comparison between an administrative database and the RIETE registry. | The aim of this study was to validate the baseline characteristics of the RIETE cohort against the much larger national Spanish population-based database. The RIETE is an ongoing registry of consecutive patients with symptomatic, objectively confirmed, acute venous thromboembolism (VTE). We compared some baseline characteristics and death rates in the administrative database from the Spanish Ministry of Health (CMBD, Conjunto Mínimo Básico de Datos) with those in the RIETE registry. During the study period, data on 87,733 patients with VTE were collected from the CMBD and 8053 from the RIETE. There were no differences between the groups in gender, mean age, clinical presentation of the VTE event, or the presence of recent surgery; however, chronic lung disease, chronic heart failure, and pregnancy were slightly more common in patients in the CMBD. There were no differences in mortality rate in patients with deep vein thrombosis, but the 12% death rate in patients with pulmonary embolism in the CMBD was three times higher than the 4.1% found in the RIETE. However, when only considering patients with pulmonary embolism who had objective tests, the 4.8% death rate in the CMBD no longer differed from the mortality in the RIETE. Our data reveal that the information in the RIETE is very close to that observed in the CMBD, thus supporting the validity of the data in the RIETE. | 18,848,178 |
Perioperative glucocorticosteroid supplementation is not supported by evidence. | Ever since the first descriptions of adrenal insufficiency following exogenous supplementation physicians dread to abolish perioperative glucocorticosteroid supplementation. Now, 55 years after the first publications we can challenge those first reports. However, these cases have resulted in the supplementation of supraphysiological doses of glucocorticosteroids to patients that use exogenous corticosteroids: the so-called perioperative glucocorticosteroid supplementation or "(gluco)corticosteroid stress scheme". It is very questionable whether a dose that exceeds the normal daily production of 5.7 mg cortisol per square meter of body surface area is necessary to prevent perioperative hypotension. Retrospective, prospective and randomised studies, though all methodologically flawed, are discussed and show that continuation of the "basal" amount of glucocorticosteroids is sufficient to counterbalance surgical stress. The current and rather defensive strategy of perioperative supraphysiological glucocorticosteroid supplementation is not embedded in medical evidence. Additionally, high doses of glucocorticosteroids have disadvantages that should not be ignored. | 18,848,181 |
Diagnosis and initial management of cerebellar infarction. | Cerebellar infarction is an important cause of stroke that often presents with common and non-specific symptoms such as dizziness, nausea and vomiting, unsteady gait, and headache. Accurate diagnosis frequently relies on careful attention to patients' coordination, gait, and eye movements--components of the neurological physical examination that are sometimes omitted or abridged if cerebellar stroke is not specifically being considered. The differential diagnosis is broad, and includes many common and benign causes. Furthermore, early-stage posterior fossa ischaemia is rarely seen with brain CT--the most commonly available initial imaging test that is used for stroke. Insufficient examination and imaging can result in misdiagnosis. However, early correct diagnosis is crucial to help prevent treatable but potentially fatal complications, such as brainstem compression and obstructive hydrocephalus. The identification and treatment of the underlying vascular lesions at an early stage can also prevent subsequent occurrences of stroke and improve patients' outcomes. Here, we review the clinical presentation of cerebellar infarction, from diagnosis and misdiagnosis to patients' monitoring, treatment, and potential complications. | 18,848,314 |
Multiplex analysis of urinary cytokine levels in rat model of cyclophosphamide-induced cystitis. | The urinary proteome is a potential easily accessible source of biomarkers for inflammatory bladder diseases, including interstitial cystitis. In the present study, we subjected rat urine to multiplex cytokine analysis in an attempt to identify an inflammatory signature of the temporal course of cyclophosphamide (CYP)-induced cystitis. Rat urine was collected for 12 hours after CYP injection (150 mg/kg) for multiplex analysis of 14 cytokines by a multiple antigen bead assay (Luminex 100 IS). Urine from each void was collected, and the voiding frequency was determined. The bladder tissue was analyzed for cytokines levels and histologic evidence of inflammation. Significant changes were noted in the urine levels of all cytokines with respect to baseline at 2, 4, 6, and 10 hours after CYP injection. Elevation was noted at all times for most cytokines, except for monocyte chemotactic protein-1, which had a 5-fold decrease at 2 hours. The urine and tissue levels of interleukin (IL)-1beta, IL-4, and growth-related oncogene/keratinocyte-derived chemokine correlated significantly, with a positive Spearman correlation also noted for granulocyte-macrophage colony-stimulating factor, monocyte chemotactic protein-1-1, IL-18, and interferon-gamma. The tissue levels for most cytokines, except for IL-2, and urinary frequency were significantly elevated in the CYP-treated rats compared with the control vehicle-treated rats. The hints of severe inflammation in the bladder indicated by the urinary cytokines were confirmed by bladder histologic examination and the tissue cytokine levels at necropsy. The progression of CYP-induced cystitis was clearly reflected in the urine matrix by the temporal and quantitative changes in the cytokine levels. Additional delineation of urine and bladder tissue cytokine expression might yield biomarkers for cystitis. | 18,848,347 |
Outcome of patients with bladder cancer with pN+ disease after preoperative chemotherapy and radical cystectomy. | Persistent nodal disease in the surgical specimen (pN+) after preoperative chemotherapy for urothelial carcinoma is associated with a poor prognosis. To improve our understanding regarding the outcomes of such patients, we performed a retrospective review of our experience. From 1993 to 2003, 857 patients underwent radical cystectomy for urothelial carcinoma of the bladder, and 150 were found to have pN+ disease. Of these 150 patients, 37 had pN+ disease despite preoperative chemotherapy and formed the basis of this report. The survival data were analyzed using the Kaplan-Meier method and Cox regression analysis. The median patient age was 66 years (range 39-85), and the median follow-up was 50 months (range 13.0-58.7). The clinical stage at the initiation of preoperative chemotherapy was cT2 with lymphovascular invasion in 7, cT3b in 6, cT4a in 4, cT4b in 2, and cN+ in 18. The 2-year overall, disease-specific, and recurrence-free survival rate was 20%, 29.2%, and 13.5%, respectively. Of the 37 patients, 11 (30%) received adjuvant chemotherapy after surgery, most (73%) were platinum-based regimens. On Kaplan-Meier analysis, adjuvant chemotherapy was associated with improved recurrence-free and disease-specific survival. On multivariate analysis, surgical margin status, sex, and histologic type were significantly associated with overall survival, and the histologic type and use of adjuvant chemotherapy were significantly associated with recurrence-free survival. Patients with persistent nodal disease despite preoperative chemotherapy have a poor prognosis. A cohort of such patients might do well with adjuvant chemotherapy. The lymph node density and pT category were not prognostic in patients with nodal metastasis after preoperative chemotherapy. | 18,848,348 |
Clinical predictors and outcomes of consistent bronchodilator response in the childhood asthma management program. | Among asthmatic subjects, bronchodilator response (BDR) to inhaled beta(2)-adrenergic agonists is variable, and the significance of a consistent response over time is unknown. We assessed baseline clinical variables and determined the clinical outcomes associated with a consistently positive BDR over 4 years in children with mild-to-moderate persistent asthma. In the 1041 participants in the Childhood Asthma Management Program, subjects with a change in FEV(1) of 12% or greater (and 200 mL) after inhaled beta(2)-agonist administration at each of their yearly follow-up visits (consistent BDR) were compared with those who did not have a consistent BDR. We identified 52 children with consistent BDRs over the 4-year trial. Multivariable logistic regression modeling demonstrated that lower baseline prebronchodilator FEV(1) values (odds ratio, 0.71; P < .0001), higher log10 IgE levels (odds ratio, 1.97; P = .002), and lack of treatment with inhaled corticosteroids (odds ratio, 0.31; P = .009) were associated with a consistent BDR. Individuals who had a consistent BDR had more hospital visits (P = .007), required more prednisone bursts (P = .0007), had increased nocturnal awakenings caused by asthma (P < .0001), and missed more days of school (P = .03) than nonresponders during the 4-year follow-up. We have identified predictors of consistent BDR and determined that this phenotype is associated with poor clinical outcomes. | 18,848,350 |
Nitrogen limited biobarriers remove atrazine from contaminated water: laboratory studies. | Atrazine is one of the most frequently used herbicides. This usage coupled with its mobility and recalcitrant nature in deeper soils and aquifers makes it a frequently encountered groundwater contaminant. We formed biobarriers in sand filled columns by coating the sand with soybean oil; after which, we inoculated the barriers with a consortium of atrazine-degrading microorganisms and evaluated the ability of the barriers to remove atrazine from a simulated groundwater containing 1 mg L(-1) atrazine. The soybean oil provided a carbon rich and nitrogen poor substrate to the microbial consortium. Under these nitrogen-limiting conditions it was hypothesized that bacteria capable of using atrazine as a source of nitrogen would remove atrazine from the flowing water. Our hypothesis proved correct and the biobarriers were effective at removing atrazine when the nitrogen content of the influent water was low. Levels of atrazine in the biobarrier effluents declined with time and by the 24th week of the study no detectable atrazine was present (limit of detection<0.005 mg L(-1)). Larger amounts of atrazine were also removed by the biobarriers; when biobarriers were fed 16.3 mg L(-1) atrazine 97% was degraded. When nitrate (5 mg L(-1) N), an alternate source of nitrogen, was added to the influent water the atrazine removal efficiency of the barriers was reduced by almost 60%. This result supports the hypothesis that atrazine was degraded as a source of nitrogen. Poisoning of the biobarriers with mercury chloride resulted in an immediate and large increase in the amount of atrazine in the barrier effluents confirming that biological activity and not abiotic factors were responsible for most of the atrazine degradation. The presence of hydroxyatrazine in the barrier effluents indicated that dehalogenation was one of the pathways of atrazine degradation. Permeable barriers might be formed in-situ by the injection of innocuous vegetable oil emulsions into an aquifer or sandy soil and used to remove atrazine from a contaminated groundwater or to protect groundwater from an atrazine spill. | 18,848,368 |
In vitro and in vivo antitumor activity of platinum(II) complexes with thiosemicarbazones derived from 2-formyl and 2-acetyl pyridine and containing ring incorporated at N(4)-position: synthesis, spectroscopic study and crystal structure of platinum(II) complexes with thiosemicarbazones, potential anticancer agents. | Reactions of thiosemicarbazones of 2-formyl and 2-acetyl pyridine and containing an azepane ring (hexamethyleneiminyl ring) incorporated at N(4)-position, HL(1) (1) and HL(2) (2) with platinum(II) afforded the complexes, [Pt(L(1))Cl] (3) and [Pt(L(2))Cl] (4). Characterization of the compounds was accomplished by means of elemental analysis and spectroscopic techniques NMR, UV-vis and IR spectroscopy. The single-crystal X-ray structure of complex [Pt(L(2))Cl] (4) shows that the ligand monoanion coordinates in a planar conformation to the metal via the pyridyl N atom, the imine-N atom, and thiolato S-atom. Compounds 1-4 have been evaluated for antiproliferative activity in vitro against three human cancer cell lines: MCF-7 (human breast cancer cell line), T24 (bladder cancer cell line), A-549 (non-small cell lung carcinoma) and a mouse L-929 (a fibroblast-like cell line cloned from strain L). Ligand 2 exhibited high activity as anticancer agent against all four cancer cell lines, while ligand 1 exhibited selectivity against MCF-7, L-929 cell lines and complex 4 against A-549, T-24 cancer cell lines. Also, the acute toxicity and antitumor activity were evaluated on leukemia P388-bearing mice. Complex 3 afforded five to six cures against leukemia P388. The in vivo results of the antitumor activity show the two platinum complexes as very effective chemotherapeutic antileukemic agents. | 18,848,372 |
Assessing joint toxicity of chemicals in Enchytraeus albidus (Enchytraeidae) and Porcellionides pruinosus (Isopoda) using avoidance behaviour as an endpoint. | Contamination problems are often characterized by complex mixtures of chemicals. There are two conceptual models usually used to evaluate patterns of mixture toxicity: Concentration Addition (CA) and Independent Action (IA). Deviations from these models as synergism, antagonism and dose dependency also occur. In the present study, single and mixture toxicity of atrazine, dimethoate, lindane, zinc and cadmium were tested in Porcellionides pruinosus and Enchytraeus albidus, using avoidance as test parameter. For both species patterns of antagonism were found when exposed to dimethoate and atrazine, synergism for lindane and dimethoate exposures (with the exception of lower doses in the isopod case study) and concentration addition for cadmium and zinc occurred, while the exposure to cadmium and dimethoate showed dissimilar patterns. This study highlights the importance of dose dependencies when testing chemical mixtures and that avoidance tests can also be used to asses the effects of mixture toxicity. | 18,848,376 |
Tracking and determinants of kidney size from fetal life until the age of 2 years: the Generation R Study. | An adverse fetal environment may lead to smaller kidneys and subsequently kidney disease and hypertension in adulthood. The aims of this study are to examine whether kidney size tracks from fetal life to childhood and whether maternal and fetal characteristics are associated with kidney size at the age of 2 years. Prospective cohort study from fetal life onward. The study was conducted in a group of 688 infants in Rotterdam, The Netherlands. Entry criteria were singleton, noncomplicated pregnancies, and Dutch ethnicity. The maternal characteristics age, height, and prepregnancy weight were measured in early pregnancy. Fetal growth, head circumference, abdominal circumference, femur length and estimated fetal weight, and placental characteristics were assessed in the second and third trimesters. Kidney size, defined as length, width, depth, and volume, was measured in the third trimester of pregnancy and at postnatal ages 6 and 24 months. Overall median gestational age was 40.3 weeks (95% range, 36.0 to 42.3 weeks), and mean birth weight was 3,536 +/- 524 (SD) g. Children tended to remain in the lowest and highest quartiles of kidney volume from the third trimester to the age of 2 years (odds ratio, 2.05; 95% confidence interval, 1.38 to 3.06; odds ratio, 3.29; 95% confidence interval, 2.22 to 4.87, respectively). Maternal height and prepregnancy weight were associated positively with kidney volume at the age of 2 years. Third-trimester fetal head circumference, abdominal circumference, and estimated weight and postnatal length were associated positively with kidney volume at the age of 2 years. Preferential fetal blood flow to the brain was associated with smaller kidneys. Kidney measurements successfully performed in only 86% of children. Small kidney size in fetal life tends to persist in early childhood. Maternal anthropometrics and fetal biometrics and blood flow patterns are associated with kidney size in childhood. Follow-up studies are needed to examine whether these variations in kidney size are related to kidney function and blood pressure in later life. | 18,848,377 |
Plasma exchange for disseminated cryptococcosis. | Acute renal failure is frequent in HIV-infected patients and may be related to HIV-associated nephropathy, drugs, or opportunistic infections. We report a peculiar case of disseminated cryptococcosis complicated by acute renal failure associated with obstruction of intrarenal capillaries by Cryptococus neoformans dead bodies and successfully treated with plasma exchanges. | 18,848,378 |
Approach for valuating the significance of laboratory simulation. | The aim of this investigation was to compare the clinical survival rate of all-ceramic FPDs with failures during in vitro simulation. 40 anterior FPDs were manufactured from lithiumdisilicate ceramic and alumina-oxide ceramic. The FPDs were adhesively bonded to human teeth and artificially aged to investigate the survival rate during thermal cycling and mechanical loading (TCML(1); 3.6 Mio*50 N ML). Survival rates were compared to available clinical data, and the TCML parameter 'mastication force' was adapted accordingly for a second TCML run (TCML(2); 3.6 Mio*25 N/35 N ML). The fracture resistance of the FPDs that survived TCML was determined. Data were statistically analysed by means of Mann-Whitney U-test, and survival rates were determined by curve fitting/regression analysis. TCML decreased survival rates by 30-50%, depending on the type of material used. Failures during TCML included cracking, chipping or fracture. Increased masticatory loading during TCML caused a higher decrease in the fracture resistance of FPDs. Fracture results were 403 N (278/453) and 426 N (317/538) for Empress 2 and 325 N (164/584) and 405 N (344/558 N) for Inceram. Despite the limitations of this study, the results indicate that TCML with 1,200,000*25/35 N provide a sufficient prognosis of probable clinical failures. Longer TCML-time with higher mastication forces may help to exclude catastrophic clinical failures. | 18,848,380 |
The pressure angle of the median nerve as a new magnetic resonance imaging parameter for the evaluation of carpal tunnel. | The purpose of this study was to compare the MRI findings of the wrists of patients with carpal tunnel syndrome (CTS) and controls. We present a new MRI parameter, the pressure angle of the median nerve, in CTS patients. The study included 55 wrists, 36 of which were diagnosed with CTS and 19 healthy controls. All subjects underwent clinical, electrophysiological, and MRI evaluation. Clinical and electrophysiological findings were staged according to the degree of deficit. MRI parameters including median nerve diameter (MR1) and width (MR2) at the pisiform bone level; median nerve diameter (MR3) and width (MR4) at the hamate bone level; carpal arch width (MR5); carpal arch height (MR6); pressure angle of the median nerve (MR7); carpal tunnel diameter at the pisiform bone level (MR8); carpal tunnel diameter at the hamate bone level (MR9) and median nerve-flattening ratio were investigated. Eighteen operated wrists were evaluated 8 weeks after surgery. Correlation between the MRI parameters, EMG and clinical signs were evaluated. Among the 36 wrists with CTS, 5.6% were mild cases, 55.6% were moderate, and 38.9% were severe. Electromyography staging was as follows: 5.6% mild, 52.8% moderate, and 41.7% severe. A good correlation between the clinical and electrophysiological staging of the wrists with CTS was demonstrated (P=0.0001). Median nerve width and carpal tunnel diameter at the pisiform bone level were found to be significantly increased whereas median nerve diameter at the hamate bone level and pressure angle of the median nerve (PAMN) were significantly lower in CTS group in comparison to controls. After surgery, median nerve diameter and width at the pisiform bone level decreased whereas median nerve diameter at the hamate bone level increased. In addition, carpal arch height and PAMN were also found to be significantly increased (P=0.0001). The carpal tunnel diameter and median nerve-flattening ratio increased at the hamate bone level post-operatively (P=0.0001) with no change at the pisiform bone level. The pressure angle of the median nerve may prove useful in the assessment of idiopathic CTS, both before and after surgery. | 18,848,388 |
Influence of pyrometallurgical copper production on the environment. | In this paper the influence of pyrometallurgical treatment of copper sulphide minerals and pyrite on the environment from the aspect of ambient air pollutions is considered. Results of emission of SO(2) and particulate matter from the location with the most pollution are presented. According to the results it could be seen that the Bor's citizen were exposed to the high concentration of SO(2) and arsenic which were found to be multiple over the Serbian legislative limits during 2007. Also, the reasons and consequences of this pollution were analysed. | 18,848,391 |
Insulin therapy in preterm newborns. | The perinatal period is known to be a critical period for pancreatic development, and the impact of prematurity on the development of insulin secretion and sensitivity is poorly defined. Premature infants are at risk of hyperglycaemia which is a marker of relative insulin deficiency which impacts on anabolism both directly and indirectly by regulation of insulin like growth factors. The use of insulin in preterm infants and prevention of hyperglycaemia could also effect immune function, lipid metabolism, growth and IGF-I generation leading to improved short term clinical outcomes such as retinopathy of prematurity. It may also have longer term health effects however the outcomes of clinical trials are currently awaited. | 18,848,411 |
Six-year change in youth physical activity and effect on fasting insulin and HOMA-IR. | There is a shortage of longitudinal data analyzing associations between physical activity and indicators of insulin resistance among children and adolescents after accounting for adiposity change. To guide future prevention efforts, data were used from the Danish arm of the European Youth Heart Study to examine these issues. Participants were 384 students in Grade 9 (aged 15 years) from the municipality of Odense, Denmark, who participated in surveys in 1997 and 2003. Physical activity was monitored for at least 3 days by accelerometer, and mean counts per minute (CPM) and minutes >3000 CPM per day were obtained. Blood samples were collected, and levels of fasting insulin, fasting glucose, and homeostasis model of assessment of insulin resistance (HOMA-IR) were obtained. Data were analyzed in 2008. Physical activity declined from 45 minutes >3000 CPM in 1997 to 35 minutes >3000 CPM in 2003. Longitudinal regression analyses showed that a change in minutes >3000 CPM was negatively associated with fasting insulin levels (z=-2.47, p=0.014) and HOMA-IR (z=-2.31, p=0.021) in 2003. Similar findings were found when CPM was used as the physical activity variable. Results demonstrated that a 6-year decline in physical activity was associated with higher insulin and HOMA-IR levels. The 6-year change in the volume of physical activity engaged in by adolescents aged 15 years was negatively associated with fasting insulin and HOMA-IR. Preventing an age-related decline in physical activity may be an effective means of preventing youth insulin resistance. | 18,848,414 |
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