title stringlengths 0 1.13k | abstract stringlengths 1 15.7k | PMID int64 22 36.5M |
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A question of class. | Fundamental misunderstandings about classification can lead scientists down unproductive or dangerous paths, argue Jeffrey Parsons and Yair Wand. | 18,948,935 |
The mental wealth of nations. | Countries must learn how to capitalize on their citizens' cognitive resources if they are to prosper, both economically and socially. Early interventions will be key. | 18,948,946 |
Inverse association between BMI and prefrontal metabolic activity in healthy adults. | Obesity has been associated with a higher risk for impaired cognitive function, which most likely reflects associated medical complications (i.e., cerebrovascular pathology). However, there is also evidence that in healthy individuals excess weight may adversely affect cognition (executive function, attention, and memory). Here, we measured regional brain glucose metabolism (using positron emission tomography (PET) and 2-deoxy-2[(18)F]fluoro-D-glucose (FDG)) to assess the relationship between BMI and brain metabolism (marker of brain function) in 21 healthy controls (BMI range 19-37 kg/m(2)) studied during baseline (no stimulation) and during cognitive stimulation (numerical calculations). Statistical parametric mapping (SPM) revealed a significant negative correlation between BMI and metabolic activity in prefrontal cortex (Brodmann areas 8, 9, 10, 11, 44) and cingulate gyrus (Brodmann area 32) but not in other regions. Moreover, baseline metabolism in these prefrontal regions was positively associated with performance on tests of memory (California Verbal Learning Test) and executive function (Stroop Interference and Symbol Digit Modality tests). In contrast, the regional brain changes during cognitive stimulation were not associated with BMI nor with neuropsychological performance. The observed association between higher BMI and lower baseline prefrontal metabolism may underlie the impaired performance reported in healthy obese individuals on some cognitive tests of executive function. On the other hand, the lack of an association between BMI and brain metabolic activation during cognitive stimulation indicates that BMI does not influence brain glucose utilization during cognitive performance. These results further highlight the urgency to institute public health interventions to prevent obesity. | 18,948,965 |
MicroRNA profile analysis of human prostate cancers. | We examined the microRNA (miRNA) expression profile of 40 prostatectomy specimens from stage T2a/b, early relapse and non-relapse cancer patients, to better understand the relationship between miRNA dysregulation and prostate oncogenesis. Paired analysis was carried out with microdissected, malignant and non-involved areas of each specimen, using high-throughput liquid-phase hybridization (mirMASA) reactions and 114 miRNA probes. Five miRNAs (miR-23b, -100, -145, -221 and -222) were significantly downregulated in malignant tissues, according to significance analysis of microarrays and paired t-test with Bonferroni correction. Lowered expression of miR-23b, -145, -221 and -222 in malignant tissues was validated by quantitative reverse transcription (qRT)-PCR analyses. Ectopic expression of these miRNAs significantly reduced LNCaP cancer cell growth, suggesting growth modulatory roles for these miRNAs. Patient subset analysis showed that those with post-surgery elevation of prostate-specific antigen (chemical relapse) displayed a distinct expression profile of 16 miRNAs, as compared with patients with non-relapse disease. A trend of increased expression (>40%) of miR-135b and miR-194 was observed by qRT-PCR confirmatory analysis of 11 patients from each clinical subset. These findings indicate that an altered miRNA expression signature accompanied the prostate oncogenic process. Additional, aberrant miRNA expression features may reflect a tendency for early disease relapse. Growth inhibition through the reconstitution of miRNAs is potentially applicable for experimental therapy of prostate cancer, pending molecular validation of targeted genes. | 18,949,015 |
Cross-regulation between herpesviruses and the TNF superfamily members. | Herpesviruses have evolved numerous strategies to subvert host immune responses so they can coexist with their host species. These viruses 'co-opt' host genes for entry into host cells and then express immunomodulatory genes, including mimics of members of the tumour-necrosis factor (TNF) superfamily, that initiate and alter host-cell signalling pathways. TNF superfamily members have crucial roles in controlling herpesvirus infection by mediating the direct killing of infected cells and by enhancing immune responses. Despite these strong immune responses, herpesviruses persist in a latent form, which suggests a dynamic relationship between the host immune system and the virus that results in a balance between host survival and viral control. | 18,949,019 |
Host cell egress and invasion induce marked relocations of glycolytic enzymes in Toxoplasma gondii tachyzoites. | Apicomplexan parasites are dependent on an F-actin and myosin-based motility system for their invasion into and escape from animal host cells, as well as for their general motility. In Toxoplasma gondii and Plasmodium species, the actin filaments and myosin motor required for this process are located in a narrow space between the parasite plasma membrane and the underlying inner membrane complex, a set of flattened cisternae that covers most the cytoplasmic face of the plasma membrane. Here we show that the energy required for Toxoplasma motility is derived mostly, if not entirely, from glycolysis and lactic acid production. We also demonstrate that the glycolytic enzymes of Toxoplasma tachyzoites undergo a striking relocation from the parasites' cytoplasm to their pellicles upon Toxoplasma egress from host cells. Specifically, it appears that the glycolytic enzymes are translocated to the cytoplasmic face of the inner membrane complex as well as to the space between the plasma membrane and inner membrane complex. The glycolytic enzymes remain pellicle-associated during extended incubations of parasites in the extracellular milieu and do not revert to a cytoplasmic location until well after parasites have completed invasion of new host cells. Translocation of glycolytic enzymes to and from the Toxoplasma pellicle appears to occur in response to changes in extracellular [K(+)] experienced during egress and invasion, a signal that requires changes of [Ca(2+)](c) in the parasite during egress. Enzyme translocation is, however, not dependent on either F-actin or intact microtubules. Our observations indicate that Toxoplasma gondii is capable of relocating its main source of energy between its cytoplasm and pellicle in response to exit from or entry into host cells. We propose that this ability allows Toxoplasma to optimize ATP delivery to those cellular processes that are most critical for survival outside host cells and those required for growth and replication of intracellular parasites. | 18,949,028 |
Evolution and dynamics of regulatory architectures controlling polymyxin B resistance in enteric bacteria. | Complex genetic networks consist of structural modules that determine the levels and timing of a cellular response. While the functional properties of the regulatory architectures that make up these modules have been extensively studied, the evolutionary history of regulatory architectures has remained largely unexplored. Here, we investigate the transition between direct and indirect regulatory pathways governing inducible resistance to the antibiotic polymyxin B in enteric bacteria. We identify a novel regulatory architecture -- designated feedforward connector loop -- that relies on a regulatory protein that connects signal transduction systems post-translationally, allowing one system to respond to a signal activating another system. The feedforward connector loop is characterized by rapid activation, slow deactivation, and elevated mRNA expression levels in comparison with the direct regulation circuit. Our results suggest that, both functionally and evolutionarily, the feedforward connector loop is the transitional stage between direct transcriptional control and indirect regulation. | 18,949,034 |
Numt-mediated double-strand break repair mitigates deletions during primate genome evolution. | Non-homologous end joining (NHEJ) is the major mechanism of double-strand break repair (DSBR) in mammalian cells. NHEJ has traditionally been inferred from experimental systems involving induced double strand breaks (DSBs). Whether or not the spectrum of repair events observed in experimental NHEJ reflects the repair of natural breaks by NHEJ during chromosomal evolution is an unresolved issue. In primate phylogeny, nuclear DNA sequences of mitochondrial origin, numts, are inserted into naturally occurring chromosomal breaks via NHEJ. Thus, numt integration sites harbor evidence for the mechanisms that act on the genome over evolutionary timescales. We have identified 35 and 55 lineage-specific numts in the human and chimpanzee genomes, respectively, using the rhesus monkey genome as an outgroup. One hundred and fifty two numt-chromosome fusion points were classified based on their repair patterns. Repair involving microhomology and repair leading to nucleotide additions were detected. These repair patterns are within the experimentally determined spectrum of classical NHEJ, suggesting that information from experimental systems is representative of broader genetic loci and end configurations. However, in incompatible DSBR events, small deletions always occur, whereas in 54% of numt integration events examined, no deletions were detected. Numts show a statistically significant reduction in deletion frequency, even in comparison to DSBR involving filler DNA. Therefore, numts show a unique mechanism of integration via NHEJ. Since the deletion frequency during numt insertion is low, native overhangs of chromosome breaks are preserved, allowing us to determine that 24% of the analyzed breaks are cohesive with overhangs of up to 11 bases. These data represent, to the best of our knowledge, the most comprehensive description of the structure of naturally occurring DSBs. We suggest a model in which the sealing of DSBs by numts, and probably by other filler DNA, prevents nuclear processing of DSBs that could result in deleterious repair. | 18,949,041 |
Resection of parosteal osteosarcoma of the distal part of the femur: an original reconstruction technique with cement and plate. | Parosteal osteosarcoma is a low-grade malignant bone tumor arising from the distal femur and tibia. Wide resection of a parosteal osteosarcoma usually prevents local recurrence. In literature, hemicortical resections of low-grade malignant bone tumors and allograft reconstruction are described. We describe a new method of resection and reconstruction of parosteal osteosarcoma located in the popliteal paraosseous space of the distal part of the femur using cement and plate (LISS-SYNTHES) through dual medial and lateral incisions. The patient did not present infections and fractures and the functional results were good. After one year, no metastases developed and there were no local recurrences. | 18,949,052 |
MicroRNA15a modulates expression of the cell-cycle regulator Cdc25A and affects hepatic cystogenesis in a rat model of polycystic kidney disease. | Hyperproliferation of bile duct epithelial cells due to cell-cycle dysregulation is a key feature of cystogenesis in polycystic liver diseases (PCLDs). Recent evidence suggests a regulatory role for microRNAs (miRNAs) in a variety of biological processes, including cell proliferation. We therefore hypothesized that miRNAs may be involved in the regulation of selected components of the cell cycle and might contribute to hepatic cystogenesis. We found that the cholangiocyte cell line PCK-CCL, which is derived from the PCK rat, a model of autosomal recessive polycystic kidney disease (ARPKD), displayed global changes in miRNA expression compared with normal rat cholangiocytes (NRCs). More specific analysis revealed decreased levels of 1 miRNA, miR15a, both in PCK-CCL cells and in liver tissue from PCK rats and patients with a PCLD. The decrease in miR15a expression was associated with upregulation of its target, the cell-cycle regulator cell division cycle 25A (Cdc25A). Overexpression of miR15a in PCK-CCL cells decreased Cdc25A levels, inhibited cell proliferation, and reduced cyst growth. In contrast, suppression of miR15a in NRCs accelerated cell proliferation, increased Cdc25A expression, and promoted cyst growth. Taken together, these results suggest that suppression of miR15a contributes to hepatic cystogenesis through dysregulation of Cdc25A. | 18,949,056 |
A role for microRNA in cystic liver and kidney diseases. | The polycystic liver and kidney diseases are a family of disorders with heterogeneous etiologies. Proposed mechanisms of disease include ciliary dysfunction, excess cell proliferation, and altered cell-cell or cell-matrix interactions. In this issue of the JCI, Lee and colleagues provide data to support a novel mechanism for cystogenesis involving microRNA (miRNA) (see the related article beginning on page 3714). They demonstrate that levels of the miRNA miR15a are decreased in livers of patients with autosomal recessive and autosomal dominant polycystic kidney disease (ARPKD and ADPKD, respectively) and congenital hepatic fibrosis as well as in the PKC rat model of ARPKD. This results in increased expression of the cell-cycle regulator Cdc25A, which is a direct target of miR15a, and increased cellular proliferation and cystogenesis in vitro. These findings suggest that other miRNAs may also participate in the molecular pathogenesis of cystic liver and kidney diseases. | 18,949,060 |
Screening Outside the Catalytic Site: Inhibition of Macromolecular Inter-actions Through Structure-Based Virtual Ligand Screening Experiments. | During these last 15 years, drug discovery strategies have essentially focused on identifying small molecules able to inhibit catalytic sites. However, other mechanisms could be targeted. Protein-protein interactions play crucial roles in a number of biological processes, and, as such, their disruption or stabilization is becoming an area of intense activity. Along the same line, inhibition of protein-membrane could be of major importance in several disease indications. Despite the many challenges associated with the development of such classes of interaction modulators, there has been considerable success in the recent years. Importantly, through the existence of protein hot-spots and the presence of druggable pockets at the macromolecular interfaces or in their vicinities, it has been possible to find small molecule effectors using a variety of screening techniques, including combined virtual ligand-in vitro screening strategy. Indeed such in silico-in vitro protocols emerge as the method of choice to facilitate our quest of novel drug-like compounds or of mechanistic probes aiming at facilitating the understanding of molecular reactions involved in the Health and Disease process. In this review, we comment recent successes of combined in silico-in vitro screening methods applied to modulating macromolecular interactions with a special emphasis on protein-membrane interactions. | 18,949,072 |
Phytochemical approach and bioanalytical strategy to develop chaperone-based medications. | Currently, no pharmaceuticals for the etiological treatment of degenerative protein-misfolding diseases (e.g., ALS, Alzheimer's or prion diseases) are commercially available. In this technical note theoretical considerations and practical approaches concerning the development of chaperone-based medications from medicinal plants (e.g., Ginkgo biloba) are reviewed and discussed in detail. Phytochaperones and other agents isolated from medicinal plants are proposed to serve as the general basis of drug development in protein-misfolding diseases. | 18,949,074 |
Properties of the SR Ca-ATPase in an Open Microsomal Membrane Preparation. | SR vesicles isolated from rabbit muscle were treated by a SDS incubation and subsequent dialysis to obtain open membrane fragments that allow a direct access to the luminal membrane surface and especially to the ion-binding sites in the P-E(2) conformation of the Ca-ATPase. The open membrane fragments showed about 80% of the enzyme activity in the untreated membranes. Pump function was investigated by using electrochromic styryl dyes. The kinetic properties of cytoplasmic ion binding showed no significant differences between the Ca-ATPases in SR vesicles and in membrane fragments. From pH-dependent Ca(2+) binding it could be deduced that due to the SDS treatment the density of negatively charged lipid was increased by one elementary charge per 12 lipid molecules. Major differences between Ca-ATPase from SR vesicles and membrane fragments were the respective fluorescence amplitudes. This effect is, however, produced by dye-lipid interaction and not by pump function. It was demonstrated that time-resolved kinetics may be study by the use of caged compounds such as caged ATP or caged calcium also in the case of the membrane fragments. | 18,949,080 |
Calculation of left ventricular relaxation time constant-Tau in patients with aortic regurgitation by continuous-wave Doppler. | Left ventricular relaxation time constant, Tau, is the best index to evaluate left ventricular diastolic function. The measurement is only available traditionally in catheter lab. In Echo lab, several methods of non-invasive measurement of Tau have been tried since 1992, however almost all the methods are still utilizing the same formula to calculate Tau as in catheter lab, which makes them inconvenient, time-consuming and sometimes not very accurate. A simple method to calculate Tau in patients with mitral regurgitation has been developed just based on Weiss' formula and simplified Bernoulli's equation. Similarly, formulas are developed here by pure mathematical derivative to calculate Tau by continuous-wave Doppler in patients with aortic regurgitation. | 18,949,095 |
Malignant conversion of a solitary papilloma in the distal trachea: report of a case. | A solitary papilloma versus the usual multiple lesions of papillomatosis is extremely rare. Even more infrequent is a solitary papilloma of the trachea in an adult patient. In the present report, a case of a solitary papilloma in the distal trachea is presented. After two unsuccessful sessions of laser ablation, resection of the lower one-third of the trachea was performed through a right posterolateral thoracotomy. Postoperative histology results disclosed a malignant degeneration into squamous cell carcinoma. The patient had an excellent outcome after resection of the affected portion of the trachea. There was no evidence of recurrence after 20 months of follow-up. | 18,949,108 |
Methacholine and PDGF activate store-operated calcium entry in neuronal precursor cells via distinct calcium entry channels. | Neurons are a diverse cell type exhibiting hugely different morphologies and neurotransmitter specifications. Their distinctive phenotypes are established during differentiation from pluripotent precursor cells. The signalling pathways that specify the lineage down which neuronal precursor cells differentiate remain to be fully elucidated. Among the many signals that impinge on the differentiation of neuronal cells, cytosolic calcium (Ca2+) has an important role. However, little is known about the nature of the Ca2+ signals involved in fate choice in neuronal precursor cells, or their sources. In this study, we show that activation of either muscarinic or platelet-derived growth factor (PDGF) receptors induces a biphasic increase in cytosolic Ca2+ that consists of release from intracellular stores followed by sustained entry across the plasma membrane. For both agonists, the prolonged Ca2+ entry occurred via a store-operated pathway that was pharmacologically indistinguishable from Ca2+ entry initiated by thapsigargin. However, muscarinic receptor-activated Ca2+ entry was inhibited by siRNA-mediated knockdown of TRPC6, whereas Ca2+ entry evoked by PDGF was not. These data provide evidence for agonist-specific activation of molecularly distinct store-operated Ca2+ entry pathways, and raise the possibility of privileged communication between these Ca2+ entry pathways and downstream processes. | 18,949,136 |
[Listeria monocytogenes infection in pregnancy: experience of Pontificia Universidad Católica de Chile University Hospital]. | Listeria monocytogenes is Gram-positive facultative intracellular pathogen often foodborne and found elsewhere. It is an uncommon cause of illness in the general population. However, it is an important cause of severe infection in neonates, pregnant women, elderly and immunosuppressed patients. Listeriosis has unique preference for pregnant women. Maternal listeriosis is a diagnostic challenge, and intrauterine infection can lead to severe complications such as amnionitis, preterm labor, spontaneous abortion, stillbirth and neonatal sepsis. From 2001 to 2005, 16 patients with L. monocytogenes were identified in this hospital; four (25%) were pregnant women. Clinical and laboratory findings are described. There were 3 preterm deliveries and 1 spontaneous second trimester abortion. Three women with listeriosis had no predisposing factors other than pregnancy. One patient was on immunosupressive drugs for ulcerative colitis. Fever was the most common symptom. Infected neonates were most commonly diagnosed with early-onset listeriosis (two cases) or fetal demise (one case). Pregnancy can be the only risk factor for listeriosis. Listeriosis should be considered during the evaluation of febrile syndrome in pregnancy as this condition can be the only risk factor. Blood and amniotic fluid cultures are useful diagnostic tests. Perinatal complications remains high. | 18,949,143 |
[Effectiveness of oral hypoglycemic drugs in the metabolic control of patients with gestational diabetes]. | Gestational Diabetes is characterized by different degrees of glucose intolerance that produce a series of fetal and perinatal alterations. During many years, in those cases of gestational diabetes that did not respond to nutritional interventions, the use of insulin was a proven treatment to achieve metabolic control and thus a better perinatal outcome. At present, some new oral hypoglycemic drugs, from the family of sulfonylureas and biguanides, have been shown to be safe, of low cost, and apparently effective in the metabolic control of this disease. We review the publications that propose the use of oral hypoglycemic drugs for the metabolic control of gestational diabetes that does not respond to nutritional measures. | 18,949,170 |
[Intestinal obstruction due to a trichobezoar or Rapunzel syndrome: report of one case]. | Rapunzel syndrome or gastrointestinal trichobezoar is caused by hair ingestion. The diagnosis may be suspected in young females with important weight loss, who deny hair eating. We report a 16 year-old female consulting in the emergency room for abdominal pain. She was subjected to an exploratory laparotomy and a big mass was palpated in the stomach. A gastrostomy and enterostomy were performed and a 17 x 6 x 5 cm trichobezoar was extracted. The patient had an uneventful postoperative outcome and was derived to Psychiatry. | 18,949,187 |
[Six minutes walk for the assessment of patients with chronic obstructive pulmonary disease]. | Exercise capacity can be evaluated in patients with chronic obstructive pulmonary disease (COPD), measuring the distance that patients are able to walk in 6 minutes (six-minute walk distance test; 6WDT). This test is simple to perform, inexpensive, reproducible and safe. It has been frequently employed for the assessment of COPD patients due to its high prognostic value of mortality and its usefulness to evaluate long-term of therapeutic interventions. In severe stages of the disease, the declining results of the best are useful to detect worsening. This review describes the method, standardization and reference values for the 6WDY and the results obtained with different therapeutic interventions, based on data from the literature and from the authors' experience. We also review its predictive value for mortality and its value in the assessment of patients with more severe COPD. | 18,949,192 |
[Strategies for changes in primary health care: evaluating the pilot implementation of the Project on Young Men's Health in Rio de Janeiro, Brazil]. | To improve young men's adherence to a teenage health care program, a project was developed and implemented with a pilot phase in primary health centers in the city of Rio de Janeiro, Brazil. This article presents the results of an evaluation performed at the end of the first year, aimed at identifying characteristics in the health care services that play a strategic role for change, as well as those that contribute to resistance. The methodology was based on participatory planning techniques and rapid assessment procedures (RAP). Considering the principles of the program's practices, a matrix was developed with five categories: implementation of the project's activities, interdisciplinary health team, health care organization, inter-sector cooperation, and user participation. Self-assessment workshops were held with the local teams. Despite good awareness among the health professionals, the project's results varied between health centers. Over-centralization and lack of flexibility appear to be related to lower capacity to incorporate new practices. Meanwhile, the health centers where specific strategies were observed also showed more successful results. | 18,949,225 |
[Use of outpatient services by the elderly in the South and Northeast of Brazil]. | This study evaluated the use of outpatient services by senior citizens (N = 4,003) drawing on data from the baseline study that evaluated the Project for Expansion and Consolidation of the Family Health Strategy (PROESF) in 41 cities in South and Northeast Brazil. Use of outpatient services was greater and more appropriate to the needs of the elderly in the South than in the Northeast. Primary care facilities in both regions met the demand by lower-income elderly, but those requiring more care were treated at other levels. The results highlight the need to increase the supply of outpatient services and ensure access by the elderly, particularly for individuals with functional impairments in the Northeast. In addition to promoting equity, primary care in both regions should adopt targeted approaches for the health needs of senior citizens. | 18,949,229 |
[Intra-urban dynamics of dengue epidemics in Belo Horizonte, Minas Gerais State, Brazil, 1996-2002]. | This study aimed to describe the temporal-spatial patterns of dengue epidemics in Belo Horizonte, Minas Gerais State, Brazil, from 1996 to 2002 and to analyze residential address as a proxy for exposure. Reported dengue cases were analyzed according to week of onset of symptoms and residential census tract. Local Moran's index was used to assess spatial autocorrelation of incidence coefficients, and recurrent census areas over different epidemic waves were also verified. Ripley's K-function was used to compare spatial distribution patterns between the two population groups, assuming that they were distributed differently around the city. A total of 99,559 dengue cases were analyzed, resulting in seven epidemic waves with different durations and intensities, with cases clustering in a small fraction of areas, thinning out both spatially and temporally. Distinct case distribution patterns were observed according to the two exposed groups, suggesting the need to improve the reporting of possible place of infection. The observed endemic pattern of the disease also requires specific strategies and poses a major challenge for health surveillance services. | 18,949,240 |
Skull radiographs and computed tomography scans in children and adolescents with mild head trauma. | To identify which pediatric patients with mild head trauma are candidates for skull radiographs or cranial computed tomography (CCT) scans. Patients with mild head trauma aged from 0 to 19 years presenting to the Emergency Department of a trauma centre from Salvador City, Brazil, between May 2007 and May 2008. A total of 1888 mild head trauma patients were admitted; mean age was 7.4 (+/-5.5) years. A total of 1956 skull radiographs and 734 CCT scans were performed. About 44.4% patients with Glasgow coma score (GCS) 13 and 55.4% with GCS 14 had abnormal CCT scans. In patients with multiple traumas, 16% had abnormal findings on CCT scans. We strongly recommend routine CCT studies to patients with GCS of 13 and 14 or to multiple trauma victims, independently of score. Routine screening skull radiographs were not useful in the evaluation of mild head trauma patients in this study. | 18,949,267 |
Psychological evaluation and cope with trigeminal neuralgia and temporomandibular disorder. | To determine the psychological aspects of orofacial pain in trigeminal neuralgia (TN) and temporomandibular disorder (TMD), and associated factors of coping as limitations in daily activities and feelings about the treatment and about the pain. 30 patients were evaluated (15 with TN and 15 with TMD) using a semi-directed interview and the Hospital Anxiety Depression (HAD) scale. TN patients knew more about their diagnosis (p<0.001). Most of the patients with TN considered their disease severe (87%), in opposite to TMD (p=0.004); both groups had a high level of limitations in daily activities, and the most helpful factors to overcome pain were the proposed treatment followed by religiosity (p<0.04). Means of HAD scores were 10.9 for anxiety (moderate) and 11.67 for depression (mild), and were not statistically different between TMD and NT (p=0.20). TN and TMD had similar scores of anxiety and depression, therefore patients consider TN more severe than TMD. Even with higher limitations, patients with TN cope better with their disease then patients with TMD. | 18,949,269 |
Urinary fluoride excretion in children exposed to fluoride toothpaste and to different water fluoride levels in a tropical area of Brazil. | The aim of this study was to evaluate the urinary fluoride excretion of 2- to 7-year-old children exposed to different water fluoride concentrations in the city of Catolé do Rocha, PB, Brazil. Forty-two children were allocated to 3 groups according to the concentration of fluoride in the water: G1 (n=10; 0.5-1.0 ppm F), G2 (n=17; 1.1-1.5 ppm F) and G3 (n= 15; >1.51 ppm F). The study was carried out in two 1-week phases with 1-month interval between the moments of data collection: in the first phase, the children used a fluoride toothpaste (FT) (1,510 ppm F) for 1 week, whereas in the second phase a non-fluoride toothpaste (NFT) was used. The urine was collected in a 24-h period in each week-phase according to Marthaler's protocol. The urinary fluoride excretion data expressed as mean (SD) in microg/24 h were: G1-FT= 452.9 (290.2); G1-NFT= 435.1 (187.0); G2-FT= 451.4 (224.0); G2-NFT= 430.3 (352.5); G3-FT=592.3 (390.5); and G3-NFT=623.6 (408.7). There was no statistically significant difference between the water fluoride groups, and regardless of the week phase (ANOVA, p>0.05). The use of fluoride toothpaste (1,510 ppmF) did not promote an increase in urinary fluoride excretion. There was a trend, though not significant, as to the increase of urine fluoride concentration in relation to fluoride concentrations in the water. The excretion values suggest that some children are under risk to develop dental fluorosis and information about the appropriate use of fluoride is necessary in this area. | 18,949,293 |
T-bar clasp-retained removable partial denture as an alternative to implant-based prosthetic treatment. | This article reports the case of a 55-year-old female patient who presented with unsatisfactory temporary crowns in the right mandibular premolars and molars, and a premolar-to-molar fixed partial denture in the left side. The clinical and radiographic examinations revealed a fracture of the left first premolar that was a retainer of the fixed partial denture and required extraction. Initially, the acrylic resin crowns were replaced by new ones, and a provisional RPD was made using acrylic resin and orthodontic wire clasps to resolve the problem arising from the loss of the fixed partial denture. Considering the patient's high esthetic demands, the treatment options for the definitive prosthetic treatment were discussed with her and rehabilitation with implant-supported dentures was proposed because the clinical conditions of the residual alveolar ridge were suitable for implant installation, and the patient's general health was excellent. However, the patient did not agree because she knew of a failed case of implant-retained denture in a diabetic individual and was concerned. The patient was fully informed that implant installation was the best indication for her case, but the arguments were not sufficient to change her decision. The treatment possibilities were presented and the patient opted for a clasp-retained removable partial denture (RPD) associated with the placement of crowns in the pillar teeth. The temporary RPD was replaced by the definitive RPD constructed subsequently. Although RPD was not the first choice, satisfactory esthetic and functional outcomes were achieved, overcoming the patient's expectations. This case report illustrates that the dentist must be prepared to deal with situations where, for reasons that cannot be managed, the patient does not accept the treatment considered as the most indicated for his/her case. Alternatives must be proposed and the functional and esthetic requirements must be fulfilled in the best possible manner. | 18,949,301 |
Cytokine profile associated with chronic and acute human schistosomiasis mansoni. | The production and regulation of interleukin (IL) IL-13, IL-4 and interferon-gamma (IFN-gamma) was evaluated in 43 schistosomiasis patients with different clinical forms. Whole-blood cultures cytokine production in response to soluble egg antigen (SEA), soluble worm adult preparation (SWAP), mitogens, neutralizing antibodies or recombinant IL-13 were measured by ELISA. After SWAP stimulation, chronic patients, particularly hepatointestinals, produced higher levels of IL-4 in comparison with acute patients, suggesting the presence of a type 2 cytokine profile in these patients. Following SEA and SWAP stimulation, hepatosplenic (HS) patients showed increased levels of IFN-gamma when compared with acute patients, indicating that HS disease in humans is associated with a type 1 cytokine response. The mechanisms of immune regulation are apparently different between the clinical stages of the disease, some of which are antigen-specific. | 18,949,326 |
Systematic identification and validation of candidate genes for detection of circulating tumor cells in peripheral blood specimens of colorectal cancer patients. | The presence of tumor cells in peripheral blood is being regarded increasingly as a clinically relevant prognostic factor for colorectal cancer patients. Current molecular methods are very sensitive but due to low specificity their diagnostic value is limited. This study was undertaken in order to systematically identify and validate new colorectal cancer (CRC) marker genes for improved detection of minimal residual disease in peripheral blood mononuclear cells of colorectal cancer patients. Marker genes with upregulated gene expression in colorectal cancer tissue and cell lines were identified using microarray experiments and publicly available gene expression data. A systematic iterative approach was used to reduce a set of 346 candidate genes, reportedly associated with CRC to a selection of candidate genes that were then further validated by relative quantitative real-time RT-PCR. Analytical sensitivity of RT-PCR assays was determined by spiking experiments with CRC cells. Diagnostic sensitivity as well as specificity was tested on a control group consisting of 18 CRC patients compared to 12 individuals without malignant disease. From a total of 346-screened genes only serine (or cysteine) proteinase inhibitor, clade B (ovalbumin), member 5 (SERPINB5) showed significantly elevated transcript levels in peripheral venous blood specimens of tumor patients when compared to the nonmalignant control group. These results were confirmed by analysis of an enlarged collective consisting of 63 CRC patients and 36 control individuals without malignant disease. In conclusion SERPINB5 seems to be a promising marker for detection of circulating tumor cells in peripheral blood of colorectal cancer patients. | 18,949,363 |
Molecular classification of brain tumor biopsies using solid-state magic angle spinning proton magnetic resonance spectroscopy and robust classifiers. | Brain tumors are one of the leading causes of death in adults with cancer; however, molecular classification of these tumors with in vivo magnetic resonance spectroscopy (MRS) is limited because of the small number of metabolites detected. In vitro MRS provides highly informative biomarker profiles at higher fields, but also consumes the sample so that it is unavailable for subsequent analysis. In contrast, ex vivo high-resolution magic angle spinning (HRMAS) MRS conserves the sample but requires large samples and can pose technical challenges for producing accurate data, depending on the sample testing temperature. We developed a novel approach that combines a two-dimensional (2D), solid-state, HRMAS proton (1H) NMR method, TOBSY (total through-bond spectroscopy), which maximizes the advantages of HRMAS and a robust classification strategy. We used approximately 2 mg of tissue at -8 degrees C from each of 55 brain biopsies, and reliably detected 16 different biologically relevant molecular species. We compared two classification strategies, the support vector machine (SVM) classifier and a feed-forward neural network using the Levenberg-Marquardt back-propagation algorithm. We used the minimum redundancy/maximum relevance (MRMR) method as a powerful feature-selection scheme along with the SVM classifier. We suggest that molecular characterization of brain tumors based on highly informative 2D MRS should enable us to type and prognose even inoperable patients with high accuracy in vivo. | 18,949,365 |
Clinical implication of glucose transport and metabolism evaluated by 18F-FDG PET in hepatocellular carcinoma. | Hepatocellular carcinoma (HCC) has variable 18F-fluoro-2-deoxy-D-glucose (18F-FDG) uptake and the relationship between 18F-FDG uptake with the expression of glucose transporters (Gluts) and hexokinase II (HK-II) has not been extensively examined. Present study explored the role of 18F-FDG positron emission tomography (PET) as a clinical significance and the association with Gluts and HK-II in patients with HCC. Whole body 18F-FDG PET, immunohistochemistry and western blot analysis of Glut-1 to Glut-5 and HK-II were performed in 31 patients (24 male and 7 female, range 48-75 years) with HCC. Significant correlation was found between 18F-FDG uptake and overall expression of Glut-2 (rho=0.55, p=0.002) and HK-II (rho=0.37, p=0.04). Expression of HK-II was correlated with Glut-2 (rho=0.57, p=0.0009) but not with other Gluts, which indicated that Glut-2 is a major glucose transporter. The prognosis of patients with SUV >/=2 and positive Glut-2 were significantly worse than that with SUV <2 and negative Glut-2 (p=0.005 and p=0.03), respectively. Multivariate analysis showed that SUV and lymph node metastasis were independent prognostic factors. The present study indicated that combined evaluation of 18F-FDG uptake and expression of Glut-2 might have an important role for management of patients with HCC. | 18,949,368 |
Caspase inhibitor decreases apoptosis in pyrogallol-treated lung cancer Calu-6 cells via the prevention of GSH depletion. | Pyrogallol (PG) is a polyphenol compound and is known to be an O2.- generator. In the present study, we evaluated the anti-apoptotic effects of caspase inhibitors in relation to changes in reactive oxygen species (ROS) and glutathione (GSH) levels in PG-treated human pulmonary adenocarcinoma Calu-6 cells. Treatment with 50 microM PG inhibited the growth of Calu-6 cells approximately 60% and induced apoptosis approximately 17% at 24 h, accompanied by mitochondrial membrane potential loss (DeltaPsim). Treatment with pan-caspase inhibitor (Z-VAD-FMK), caspase-3 inhibitor (Z-DEVD-FMK), caspase-8 inhibitor (Z-IETD-FMK) and caspase-9 inhibitor (Z-LEHD-FMK) significantly prevented apoptosis in PG-treated Calu-6 cells at 24 h. PG increased the ROS and depleted GSH contents in Calu-6 cells. Treatment with each caspase inhibitor did not significantly change the ROS and GSH levels in PG-treated Calu-6 cells at 24 h. However, Z-VAD significantly prevented GSH depletion in PG-treated Calu-6 cells at the late time phase of 72 h. Conclusively, the anti-apoptotic effect of caspase inhibitor on PG-induced Calu-6 cell death was closely related to changes in GSH content rather than ROS levels. | 18,949,374 |
Co-targeting the EGFR and IGF-IR with anti-EGFR monoclonal antibody ICR62 and the IGF-IR tyrosine kinase inhibitor NVP-AEW541 in colorectal cancer cells. | The aberrant expression of the epidermal growth factor receptor (EGFR) has been reported in a wide range of epithelial tumours. In some studies, co-expression of insulin-like growth factor receptor-I (IGF-IR) have been associated with resistance to the EGFR inhibitors. Here, we investigated the sensitivity of a panel of human colorectal tumour cell lines, including two newly established lines Colo2 and Colo13, to treatment with anti-EGFR mAb ICR62 and IGF-IR tyrosine kinase inhibitor NVP-AEW541 alone and in combination. We also determined the association between the expression levels of EGFR and IGF-IR with their responses to ICR62 and/or NVP-AEW541. In contrast to DiFi cells, which contained high levels of EGFR but lower level of IGF-IR, the remaining 11 colorectal tumour cells expressed low levels of both EGFR and IGF-IR and such cells were relatively resistant to ICR62 or NVP-AEW-541 when used alone. Interestingly, compared to the results with the single agent, the effect of combination of NVP-AEW541 and ICR62 was found to be additive on inhibiting the growth of Colo13, CCL235, CCL244 cells but antagonistic in other (CCL218) cells. While overexpression of the EGFR seems to be associated with response to ICR62, no clear correlation was found between the expression levels of EGFR and IGF-IR, or the levels of phosphorylated EGFR and response to treatment with NVP-AEW541, in single or combination setting with ICR62. Our results suggest that combining EGFR and IGF-IR inhibitors may enhance antitumour response in a fraction of colorectal cancer cells and warrants further study in colorectal cancer. | 18,949,375 |
The histone-deacetylase inhibitor MS-275 and the CDK-inhibitor CYC-202 promote anti-tumor effects in hepatoma cell lines. | Effective therapies for advanced stages of hepatocellular carcinoma (HCC) have yet to be developed. We investigated how far a combination of the HDAC inhibitor MS-275 and the CDK inhibitor CYC-202 synergizes to inhibit proliferation and promotes apoptosis of hepatoma cells in vitro. Human hepatoma cell lines Hep3B and HepG2 as well as primary human foreskin fibroblasts as non-malignant controls were cultured under standardized conditions and incubated with increasing concentrations of CYC-202 and MS-275 as single agents and in combination. After 24 to 72 h, apoptosis was analyzed by flow cytometry (propidium iodide, JC-1) and by immunocytochemistry for cytokeratin 18 fragmentation. DNA synthesis was assessed using bromodeoxyuridine incorporation. Protein was separated for Western blotting against p21, bax and bcl-2 and fluorimetric activity assays against caspase 3 and 8. The results showed that the combination of CYC-202 and MS-275 leads to better pro-apoptotic effects than the employment of single substances. Apoptosis was induced via the mitochondrial pathway as evidenced by a shift in the bax/bcl-2 ratio and breakdown of mitochondrial transmembrane potentials. Caspase assays revealed a strong induction of caspase 3 but not of the extrinsic initiator caspase 8. In conclusion, combination therapy with the biomodulators MS-275 and CYC-202 is a promising treatment option for HCC. | 18,949,429 |
The aberrant promoter methylation of BMP3b and BMP6 in malignant pleural mesotheliomas. | Bone morphogenetic proteins (BMPs) belong to the transforming growth factor-beta superfamily. Recent studies have showed that aberrant methylation of BMP genes is present in several types of human cancer. We examined the expression and methylation status of BMP3b and BMP6 in malignant pleural mesotheliomas (MPMs). The expression status of BMP3b, and BMP6 mRNAs were examined in seven MPM cell lines by RT-PCR assay. The expression of BMP3b was completely suppressed in 2 and partially suppressed in 2 of 7 cell lines and expression of BMP6 was partially suppressed in 2 cell lines. Methylation status of BMP3b in cell lines was determined by methylation-specific assay to find aberrant methylation in 6 cell lines which include 4 cell lines with suppressed BMP3b expression. Partial methylation of BMP6 was found in 2 cell lines whose expression was partially suppressed. Treatment with 5-Aza-dC restored BMP3b expression in methylated cell lines. Next, we examined the methylation status in 57 surgically resected MPM cases and found aberrant methylation of BMP3b in 9 (53%) out of 17 cases from Japan and 3 (8%) of 40 cases from USA and that of BMP6 in 4 (24%) cases from Japan and 12 (30%) cases from USA, showing significant difference in frequency of BMP3b methylation between MPMs of the two countries (P=0.0004). Our study indicated that BMP3b and BMP6 genes were suppressed by DNA methylation and methylation of BMP3b is significantly frequent in Japanese MPMs, suggesting its pathogenic role and the ethnic difference in MPMs. | 18,949,431 |
Usefulness of DNA barcoding in ecotoxicological investigations: resolving taxonomic uncertainties using Eisenia malm 1877 as an example. | Standard test species may differ in their response to toxicants. Accurate identification of test organisms is therefore of critical importance in correctly interpreting data generated from laboratory assays. This is not always possible when species are morphologically similar or where the taxonomy of the group has recently been revised. A case in hand concerns Eisenia sp. Based on recent genetic evidence two species, Eisenia andrei and Eisenia fetida, which were previously considered a single species, are currently recognized. In these instances, DNA barcoding, demonstrated and discussed herein, provides a method to accurately identify test organisms. | 18,949,437 |
Electroporation microarray for parallel transfer of small interfering RNA into mammalian cells. | This paper describes the fabrication of microarrays that enable the parallel electroporation of small interfering RNAs (siRNAs) into mammalian cells. To optimize the conditions of microarray preparation and electric pulsing, a self-assembled monolayer was formed on a gold electrode, and a cationic polymer was adsorbed by the entire surface of the monolayer. siRNA was then adsorbed by the cationically modified electrode through electrostatic interactions. Human embryonic kidney cells stably transformed with the expression construct of green fluorescent protein (GFP) were used to examine the electric pulse-triggered transfer of GFP-specific siRNA. A single electric pulse was applied to the cells cultured on the electrode at a field strength of 240 V cm(-1). The expression of GFP was significantly suppressed in a sequence-specific manner two days after pulsing. Microscopic observation and flow-cytometric analysis revealed that the expression of GFP was attenuated in the majority of cells in a loading-dependent manner. Moreover, the effect of siRNA could be temporally controlled by changing the culture periods before pulsing. When a micropatterned self-assembled monolayer was used as a platform for loading siRNA in an array format, gene silencing was spatially restricted to the regions where specific siRNA was loaded. From these results, we conclude that array-based electroporation provides an excellent means of individual transfer of siRNAs into mammalian cells for high-throughput gene function studies. | 18,949,467 |
afsQ1-Q2-sigQ is a pleiotropic but conditionally required signal transduction system for both secondary metabolism and morphological development in Streptomyces coelicolor. | Two-component system AfsQ1-Q2 of Streptomyces coelicolor was identified previously for its ability to stimulate actinorhodin (ACT) and undecylprodigiosin (RED) production in Streptomyces lividans. However, disruption of either afsQ1 or afsQ2 in S. coelicolor led to no detectable changes in secondary metabolite formation or morphogenesis. In this study, we reported that, when cultivated on defined minimal medium (MM) with glutamate as the sole nitrogen source, the afsQ mutant exhibited significantly decreased ACT, RED, and calcium-dependent antibiotic (CDA) production and rapid growth of aerial mycelium. In addition, we also found that deletion of sigQ, which is located upstream of afsQ1-Q2 and encodes a putative sigma factor, led to the precocious hyperproduction of these antibiotics and delayed formation of sporulating aerial mycelium in the same glutamate-based defined MM. Reverse-transcription polymerase chain reaction and egfp fusion analyses showed that the expression of sigQ was under control by afsQ. In addition, deletion of both afsQ-sigQ resulted in the phenotype identical to that of afsQ mutant. The results suggested that afsQ1-Q2 and sigQ worked together in the regulation of both antibiotic biosynthesis and morphological development, and sigQ might be responsible for antagonizing the function of AfsQ1-Q2 in S. coelicolor, however, in a medium-dependent manner. Moreover, the study showed that the medium-dependent regulation of antibiotic biosynthesis by AfsQ1-Q2-SigQ was through pathway-specific activator genes actII-ORF4, redD, and cdaR. The study provides new insights on regulation of antibiotic biosynthesis and morphological development in S. coelicolor. | 18,949,475 |
Expression of somite segmentation genes in amphioxus: a clock without a wavefront? | In the basal chordate amphioxus (Branchiostoma), somites extend the full length of the body. The anteriormost somites segment during the gastrula and neurula stages from dorsolateral grooves of the archenteron. The remaining ones pinch off, one at a time, from the tail bud. These posterior somites appear to be homologous to those of vertebrates, even though the latter pinch off from the anterior end of bands of presomitic mesoderm rather than directly from the tail bud. To gain insights into the evolution of mesodermal segmentation in chordates, we determined the expression of ten genes in nascent amphioxus somites. Five (Uncx4.1, NeuroD/atonal-related, IrxA, Pcdhdelta2-17/18, and Hey1) are expressed in stripes in the dorsolateral mesoderm at the gastrula stage and in the tail bud while three (Paraxis, Lcx, and Axin) are expressed in the posterior mesendoderm at the gastrula and neurula stages and in the tail bud at later stages. Expression of two genes (Pbx and OligA) suggests roles in the anterior somites that may be unrelated to initial segmentation. Together with previous data, our results indicate that, with the exception that Engrailed is only segmentally expressed in the anterior somites, the genetic mechanisms controlling formation of both the anterior and posterior somites are probably largely identical. Thus, the fundamental pathways for mesodermal segmentation involving Notch-Delta, Wnt/beta-catenin, and Fgf signaling were already in place in the common ancestor of amphioxus and vertebrates although budding of somites from bands of presomitic mesoderm exhibiting waves of expression of Notch, Wnt, and Fgf target genes was likely a vertebrate novelty. Given the conservation of segmentation gene expression between amphioxus and vertebrate somites, we propose that the clock mechanism may have been established in the basal chordate, while the wavefront evolved later in the vertebrate lineage. | 18,949,486 |
Arbuscular mycorrhizal symbiosis increases host plant acceptance and population growth rates of the two-spotted spider mite Tetranychus urticae. | Most terrestrial plants live in symbiosis with arbuscular mycorrhizal (AM) fungi. Studies on the direct interaction between plants and mycorrhizal fungi are numerous whereas studies on the indirect interaction between such fungi and herbivores feeding on aboveground plant parts are scarce. We studied the impact of AM symbiosis on host plant choice and life history of an acarine surface piercing-sucking herbivore, the polyphagous two-spotted spider mite Tetranychus urticae. Experiments were performed on detached leaflets taken from common bean plants (Phaseolus vulgaris) colonized or not colonized by the AM fungus Glomus mosseae. T. urticae females were subjected to choice tests between leaves from mycorrhizal and non-mycorrhizal plants. Juvenile survival and development, adult female survival, oviposition rate and offspring sex ratio were measured in order to estimate the population growth parameters of T. urticae on either substrate. Moreover, we analyzed the macro- and micronutrient concentration of the aboveground plant parts. Adult T. urticae females preferentially resided and oviposited on mycorrhizal versus non-mycorrhizal leaflets. AM symbiosis significantly decreased embryonic development time and increased the overall oviposition rate as well as the proportion of female offspring produced during peak oviposition. Altogether, the improved life history parameters resulted in significant changes in net reproductive rate, intrinsic rate of increase, doubling time and finite rate of increase. Aboveground parts of colonized plants showed higher concentrations of P and K whereas Mn and Zn were both found at lower levels. This is the first study documenting the effect of AM symbiosis on the population growth rates of a herbivore, tracking the changes in life history characteristics throughout the life cycle. We discuss the AM-plant-herbivore interaction in relation to plant quality, herbivore feeding type and site and the evolutionary implications in a multi-trophic context. | 18,949,488 |
Determination of triacylglycerols in butterfat by normal-phase HPLC and electrospray-tandem mass spectrometry. | Here, we report the identification and quantification of the molecular species of long-, medium-, and short-chain triacylglycerols (TAG) in butterfat (BF), including TAG with an odd number of acyl carbons (ACN) and TAG with unidentified molecular species. In the present study, in addition to auto-MS(2), a large number of methods, each recording MS(2) for 1-4 ions, were used for identification of TAG species. For the quantification of long-chain, odd ACN TAG, and TAG with unidentified molecular species, molar correction factors (MCF) were calculated from the uncorrected mol% (area mol%) of each ACN:DB (number of double bonds) class in randomized butterfat (RBF), and the respective mol% in the calculated random composition of RBF. The butyrate, caproate, and medium-chain (C(8), C(10)) TAG were quantified using regio- or acyl-chain-specific MCF calculated from their area mol% in RBF and mol% in the calculated random composition. These methods enabled us to identify ca. 450 TAG species in 184 quantified peaks of 88 ACN:DB classes. The proportions of saturated, monoene, diene, triene, tetraene, pentaene, and hexaene TAG were 40.0, 38.4, 16.2, 4.5, 0.6, 0.1, and 0.03 mol%, respectively. The proportions of TAG with not identified molecular species and odd ACN TAG were 11.8 and 5.7 mol%, respectively. The most abundant short-chain TAG species were butyroyldipalmitoylglycerol + butyroylmyristoylstearoylglycerol (5.25 mol%) and butyroylpalmitoyloleoylglycerol (4.08 mol%). | 18,949,502 |
Detection of artificial occlusal caries in a phosphor imaging plate system with two types of LCD monitors versus three different films. | The aim of this study was to determine diagnostic performance of a storage phosphor plate system Digora Optime (Soredex, Helsinki, Finland) with two types of LCD monitor in the detection of artificial caries when compared to Ultraspeed (D), Ektaspeed Plus (E), and Insight (F) radiographic films. Seventy extracted human molars-with artificial caries-were radiographed under identical standardized conditions using (1) a storage phosphor plate system Digora (Soredex, Helsinki, Finland), (2) Insight, (3) Ektaspeed Plus, and (4) Ultraspeed (Carestream Health Inc, Rochester, NY). All digital images and radiographs were examined by three observers for the presence or absence of artificial caries using a five-point confidence scale. Digital images were evaluated both on a LCD computer monitor (Philips 170S, Holland) and medical monitor-3 megapixel monochrome display (Me355i2, Totoku, Tokyo)-with brightness and contrast enhancement. Observer responses were evaluated using ROC analysis and other measurements for diagnostic accuracy. Storage phosphor images with medical monitor demonstrated higher mean A (z) values (0.70 +/- 0.08) than digital images with computer monitor and conventional films. Storage phosphor images with medical monitor presented the highest score, 0.97, 0.90, 0.94, for each observer, respectively. Also, true positive observations (0.82) and positive likelihood ratios (2.71) were higher in enhanced storage phosphor images with medical monitor. Caries detection of mechanically created lesions by experienced radiologists is roughly comparable when examining D-speed film images and Digora images on both the computer and medical LCD monitors, and appears to be poorer on E- and F-speed film images. | 18,949,518 |
Poly (ADP-ribose) polymerase inhibition improves endothelial dysfunction induced by hyperhomocysteinemia in rats. | We investigated the possible protective effect of poly (ADP-ribose) polymerase (PARP) inhibition in preventing endothelial dysfunction induced by hyperhomocysteinemia (Hhcy). Sprague-Dawley rats were divided into Hhcy group, Hhcy + 3-aminobenzamide(3-AB) group, control group and control + 3-AB group. A high-methionine diet was given to induce hyperhomocysteinemia. In Hhcy + 3-AB and control + 3-AB groups, rats were injected intraperitoneally with 3-AB (inhibitor of PARP). After 45 days, ultrastructural changes of aortas were observed by transmission electron microscope. Vascular reactivity of thoracic aortic rings was measured in organ chambers. PARP activity was detected. The levels of plasma total homocysteine, nitrite/nitrate, endothelin (ET)-1 and malondialdehyde were assayed. Rats in Hhcy group developed severe hyperhomocysteinemia and significant loss of endothelial function as measured by both vascular rings and levels of nitrite/nitrate and ET-1. Malondialdehyde levels increased significantly in Hhcy rats compared with control rats. 3-AB improved Ach-induced, NO-mediated vascular relaxation and stabilized the level of nitrite/nitrate and ET-1. Obvious improvement of ultrastructure can be observed in Hhcy + 3-AB group. These results suggest that pharmacological inhibition of PARP prevents the development of endothelial dysfunction in rats with hyperhomocysteinemia which may represent a novel approach to improve vascular dysfunction associated with hyperhomocysteinemia. | 18,949,543 |
Leukotriene signaling in atherosclerosis and ischemia. | The inflammatory process of atherosclerosis is associated with several pathophysiological reactions within the vascular wall. The arachidonic acid released by phospholipase A(2) serves as substrate for the production of a group of lipid mediators known as the leukotrienes, which induce pro-inflammatory signaling through activation of specific BLT and CysLT receptors. Leukotriene signaling has been implicated in early lipid retention and foam cell accumulation, as well as in the development of intimal hyperplasia and advanced atherosclerotic lesions. Furthermore, the association of leukotrienes with degradation of extracellular matrix has suggested a role in atherosclerotic plaque rupture. Finally, studies of either myocardial or cerebral ischemia and reperfusion indicate that leukotriene signaling in addition may be involved in the development of ischemic injury. Both leukotriene synthesis inhibitors and leukotriene receptor antagonists have been suggested to induce beneficial effects at different stages of the atherosclerosis process. | 18,949,546 |
Kaempferol induces cell death through ERK and Akt-dependent down-regulation of XIAP and survivin in human glioma cells. | The present study was undertaken to determine the molecular mechanism by which kaempferol induces cell death in human glioma cells. Kaempferol resulted in loss of cell viability and inhibition of proliferation in a dose- and time-dependent manner, which were largely attributed to cell death. Kaempferol caused an increase in reactive oxygen species (ROS) generation and the kaempferol-induced cell death was prevented by antioxidants, suggesting that ROS generation is involved in kaempferol-induced cell death. Kaempferol caused depolarization of mitochondrial membrane potential. Western blot analysis showed that kaempferol treatment caused a rapid reduction in phosphorylation of extracellular signal-regulated kinase (ERK) and Akt. The ERK inhibitor U0126 and the Akt inhibitor LY984002 increased the kaempferol-induced cell death and overexpression of MEK, the upstream kinase of ERK, and Akt prevented the cell death. The expression of anti-apoptotic proteins XIAP and survivin was down-regulated by kaempferol and its effect was prevented by overexpression of MEK and Akt. Kaempferol induced activation of caspase-3 and kaempferol-induced cell death was prevented by caspase inhibitors. Taken together, these findings suggest that kaempferol results in human glioma cell death through caspase-dependent mechanisms involving down-regulation of XIAP and survivin regulating by ERK and Akt. | 18,949,556 |
Predicting recreational difficulties and decreased leisure activities in women 6-12 months post breast cancer surgery. | A Canadian research team is conducting a multi-centered, non-interventional national study with the objective of charting the course of arm morbidity after breast cancer surgery. This paper examined the relationship between arm morbidity and leisure and recreational activities of affected women. Five hundred and forty seven women with stage I-III breast cancer were recruited in four centers across Canada: Surrey (BC); Winnipeg (MB), Montreal (QB) and Fredericton (NB). Participants were enrolled in the study 6-12 months post surgery. Physical examination was used to assess arm and shoulder functioning and questionnaires were used to assess disability, pain, and participation in recreational and leisure activities. At the first clinical assessment (T1), the mean number of months post breast cancer surgery was 8.4. At T1 49% of women reported difficulty with recreational activities that involved "some force or impact" and 29% experienced negative changes to their involvement in leisure activities. A hierarchical multiple regression analysis found that several arm morbidity variables were significant predictors of difficulty with participation in recreational activities. A second hierarchical regression found also that arm morbidity factors were significant predictors of negative changes in leisure activities. Follow-up analyses found that arm morbidity, was most closely related to difficulty with recreational activities requiring free movement of the arm and using force. Many women treated for breast cancer experience arm morbidity. Arm morbidity is related to difficulties with recreational activities and negative changes in leisure activity participation. Breast cancer survivors should engage in recreational and leisure activities that are compatible with reduced range of motion and pain, and avoid those that exacerbate their arm morbidity. | 18,949,564 |
Mineral profiling of local pig-feeds and pigs reared under resource driven production system to reduce porcine mineral deficiency in subtropical hill ecosystem of Northeastern India. | The present study assessed the mineral status of pigs fed with local feed resources. The commonly used plants for feeding pigs and blood serum samples from Hampshire, Large White Yorkshire and indigenous pigs were analyzed for total protein, albumin and cholesterol levels. Processed plant and serum samples were also analyzed for calcium, phosphorus, magnesium, sodium, potassium, copper, cobalt, manganese, iron and zinc. The incidence and extent of mineral deficiency in pigs was quantified. No significant difference was observed in total protein and albumin levels between any two breed/types of pigs, however the Indigenous pigs showed significantly (P < 0.05) higher cholesterol level compared to other two breeds. Among different plants, Spilanthus sp had majority of macro and micro nutrients in high levels. Regarding incidence of mineral deficiency in pigs, it was observed that 90, 67.1, 61.4, 48.6, 95.7% of the pigs were deficient in calcium, phosphorus, sodium, magnesium and potassium. An interesting finding was that all the pigs (100%) utilized in the study were deficient in zinc. From this study, it was inferred that there are good numbers of potential source of mineral that might be used more economically to improve the mineral availability to pigs. | 18,949,573 |
Male-female differences in the risk of tuberculosis in dialysis patients. | To define any gender-related differences in the prevalence and risk for tuberculosis (TB) in hemodialysis (HD) patients. All active TB cases were recorded during a 36-month follow-up of 272 (193 male and 79 female) HD patients. Entering the study, HD patients were tested with tuberculin and 2,4-dinitrochlorobenzene, and a cell-mediated immunity (CMI) index was estimated. Relative risks (RR) for TB were calculated considering subjects from the background general population as a reference group. The independent effect of age, BMI and tuberculin sensitivity was determined using Cox's proportional hazard model. Female HD patients presented significantly lower CMI indices and rates of positive Mantoux tests, but higher rates of DM, as compared to males. The male:female ratio in TB for the general and HD patients population was 1.8 and 0.6, respectively. There was a significantly lower TB prevalence in male as compared to female HD patients (7.7% vs. 11.3%), and a subsequent female predominance in risk for TB in those HD patients aged <49 and 50-69 years (M:F adjusted relative risk 0.67 and 0.53) was recorded. In contrast to the general population, there is a female predominance among dialysis TB patients younger than 70 years associated with the coexistence of DM. Female gender should always be considered as a risk factor when evaluating diabetic HD patients for active TB. | 18,949,574 |
Tetrahydrobiopterin deficiency in human rabies. | Rabies is a fatal viral encephalitis characterized by a clinically acute and progressive course. With rare exceptions, there is a discrepancy between clinical outcome and frank histological alterations in rabies. Investigators have postulated that rabies virus may modify neurotransmission through occupancy of cellular receptors or alteration of ion channels. We took advantage of these observations to improvise a successful therapy for rabies. The Milwaukee protocol ( www.mcw.edu/rabies ) was further modified to treat two German patients. We measured pterins and monoamine neurotransmitter metabolites in the CSF of patients with rabies by HPLC with electrochemical or fluorescent detection. We report loss of tetrahydrobiopterin (BH(4)) and associated pathological decrease of dopaminergic and serotoninergic neurotransmission in three successive patients with rabies. CSF levels of BH(4) and neurotransmitter metabolites increased in two patients who were supplemented. Our findings support the long-standing speculation of modified neurotransmission in the pathogenesis of rabies, but by another mechanism. Brain turnover of dopamine and serotonin is reduced following rabies-acquired BH(4) deficiency. Neuronal nitric oxide synthase is BH(4)-dependent and may also be involved, possibly causing cerebrovascular insufficiency in one patient. This work must be carefully replicated in animal models and future patients. We are cautiously optimistic at the prospect of readily available, metabolically specific, enteral therapy for rabies. | 18,949,578 |
Health-related quality of life and utilities in primary-care patients with generalized anxiety disorder. | Generalized anxiety disorder (GAD) is prevalent and significantly impacts patient health-related quality of life (HRQL) and disability. This study evaluated the effect of GAD and anxiety symptom severity on the HRQL of primary-care patients with GAD. Patients 18 years or older with GAD were recruited from an integrated health care delivery system. Clinical assessments included the Hamilton Anxiety Rating Scale (HAM-A), GAD Questionnaire-IV (GAD-Q-IV), and the Patient Health Questionnaire depression module (PHQ). HRQL was assessed by the Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF), Sheehan Disability Scale (SDS), SF-12 Health Survey (SF-6D), and the Health Utilities Index (HUI2, HUI3). The sample included 297 patients, 72% women with mean +/- standard deviation (SD) age of 47.6 +/- 13.7 years. At baseline, the mean HAM-A score was 16.8 +/- 7.6 (suggesting the presence of moderate anxiety symptoms). Anxiety and depression symptoms were significantly correlated with mental component summary (MCS), Q-LES-Q-SF, SDS, SF-6D, HUI2, and HUI3 scores (all P < 0.001). The mean HRQL and all of the preference-based measures varied significantly by anxiety severity groups (all P < 0.001). Anxiety and depression symptoms significantly predicted HRQL and preference-based scores (R(2) values ranged from 0.22 to 0.57). Anxiety symptoms reported by GAD patients resulted in significant impairment to HRQL and functional outcomes. | 18,949,580 |
Cytogenetic characterisation in Chinese patients with chronic lymphocytic leukemia: a prospective, multicenter study on 143 cases analysed with interphase fluorescence in situ hybridisation. | Chronic lymphocytic leukemia (CLL) is infrequent in Chinese people. Conventional cytogenetic analysis underestimates the frequency of chromosome aberrations in CLL due to the low rate of spontaneous mitoses. The aim of this study was to prospectively explore the frequency of chromosomal abnormalities in Chinese patients with CLL using interphase fluorescence in situ hybridisation (FISH) and probes for 12 centromere, 13q14, 14q32, 17p13, 11q22 and 6q23 on 143 patients with CLL. Molecular cytogenetic aberrations were found in 104 patients (72.7%) and 40 patients (28.0%) with more than two abnormalities. The most frequent abnormality was del(13q14) (47.6%), followed by trisomy 12 (21.7%), 14q32 translocation (19.6%), del(17p13) (12.6%), del(11q22) (11.9%) and del(6q23) (4.9%), respectively. The percentages of patients with aberrations by FISH were 75.4%, 72.3% and 67.7% for Binet stages A, B and C, respectively. In early stage (Binet A), del(13q14) aberration was more frequent than in Binet B and C (61.5% vs. 31.9% and 41.9%) (P=0.021). Patients with advanced stage (Binet C) had more frequent del(17p13) aberration than in Binet A and B (32.3% vs. 9.2% and 4.3%) (P=0.008). It was showed that the frequencies of the chromosomal abnormalities in our study population were similar to the frequencies in Western countries. | 18,949,612 |
Feasibility of allogeneic hematopoietic stem cell transplantation for follicular lymphoma undergoing transformation to diffuse large B-cell lymphoma. | The transformation of follicular lymphoma (FL) to high-grade histology occurs in up to 70% of FL patients. Studies reporting outcomes of transformed FL patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) are scant. Eight FL patients with histologically confirmed transformation to diffuse large B-cell lymphoma underwent HSCT at our institution. The median age was 56 years (range 44-63 years). Median follow-up is 60 months. Progression free survival and overall survival at 4-years for patients undergoing allogeneic HSCT is 56% and 66%, respectively. Four patients developed grade II-IV acute GVHD, whereas four patients had extensive chronic GVHD. Day 100 and overall non-relapse mortality rate was 12.5% and 25%, respectively. Allogeneic HSCT appears feasible in patients with transformed FL and is associated with acceptable treatment-related mortality and low relapse rates. | 18,949,613 |
Developing linear ADL ability measures based on the ADL Taxonomy: a Rasch analysis. | The aim of this pilot study was to explore the possibility of developing linear measures of ADL ability based on the ADL Taxonomy and a three-category rating scale. Data were obtained from medical records of adults with moderate to severe brain injury. The participants were rated on the ADL taxonomy, and recorded on the ADL Taxonomy Circle, based on direct observations. By applying the Rasch rating scale model, we examined the possibility of converting the raw ordinal scores into equal-interval estimates of the participants' ADL ability. The data analysis indicated that the rating scale used in this study displays sound psychometric properties. Items from the ADL taxonomy defined one construct after 10 actions were removed, but retention of all items did not disrupt the measurement system. Except for one item in each of five different activity domains, the item difficulty hierarchy was the same as in the hierarchy originally published, supporting reliability of the item difficulty estimates. The ADL taxonomy discriminated well between different levels of ability in this sample of persons with brain injury. This preliminary study indicates that the ADL taxonomy has potential to become a linear measure of a person's ability to perform ADL tasks. | 18,949,630 |
What factors explain the differences in morbidity estimations among general practice registration networks in the Netherlands? A first analysis. | Information on the incidence and prevalence of diseases is a core indicator for public health. There are several ways to estimate morbidity in a population (e.g., surveys, healthcare registers). In this paper, we focus on one particular source: general practice based registers. Dutch general practice is a potentially valid source because nearly all non-institutionalized inhabitants are registered with a general practitioner (GP), and the GP fulfils the role as "gatekeeper". However, there are some unexplained differences among morbidity estimations calculated from the data of various general practice registration networks (GPRNs). To describe and categorize factors that may explain the differences in morbidity rates from different GPRNs, and to provide an overview of these factors in Dutch GPRNs. Four categories of factors are distinguished: "healthcare system", "methodological characteristics", "general practitioner", and "patient". The overview of 11 Dutch GPRNs reveals considerable differences in factors. Differences in morbidity estimation depend on factors in the four categories. Most attention is dedicated to the factors in the "methodology characteristics" category, mainly because these factors can be directly influenced by the GPRN. | 18,949,646 |
World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for the pharmacological treatment of anxiety, obsessive-compulsive and post-traumatic stress disorders - first revision. | In this report, which is an update of a guideline published in 2002 (Bandelow et al. 2002, World J Biol Psychiatry 3:171), recommendations for the pharmacological treatment of anxiety disorder, obsessive-compulsive disorder (OCD) and post-traumatic stress disorder (PTSD) are presented. Since the publication of the first version of this guideline, a substantial number of new randomized controlled studies of anxiolytics have been published. In particular, more relapse prevention studies are now available that show sustained efficacy of anxiolytic drugs. The recommendations, developed by the World Federation of Societies of Biological Psychiatry (WFSBP) Task Force for the Pharmacological Treatment of Anxiety, Obsessive-Compulsive and Post-traumatic Stress Disorders, a consensus panel of 30 international experts, are now based on 510 published randomized, placebo- or comparator-controlled clinical studies (RCTs) and 130 open studies and case reports. First-line treatments for these disorders are selective serotonin reuptake inhibitors (SSRIs), serotonin-noradrenaline reuptake inhibitors (SNRIs) and the calcium channel modulator pregabalin. Tricyclic antidepressants (TCAs) are equally effective for some disorders, but many are less well tolerated than the SSRIs/SNRIs. In treatment-resistant cases, benzodiazepines may be used when the patient does not have a history of substance abuse disorders. Potential treatment options for patients unresponsive to standard treatments are described in this overview. Although these guidelines focus on medications, non-pharmacological were also considered. Cognitive behavioural therapy (CBT) and other variants of behaviour therapy have been sufficiently investigated in controlled studies in patients with anxiety disorders, OCD, and PTSD to support them being recommended either alone or in combination with the above medicines. | 18,949,648 |
Pediatric fatality secondary to EDTA chelation. | Chelation therapy has emerged as a popular treatment modality to remove heavy metals that are thought to cause autism. We report a fatality that occurred as a consequence of chelation therapy for autism when the incorrect form of EDTA was administered. A five-year-old autistic male was being chelated in a physician's office. While receiving his third treatment he went into cardiac arrest. It was not determined until after the child's death that he had been given edetate disodium rather than edetate calcium disodium, causing profound hypocalcemia and triggering the cardiac events that led to his death. In 1991, the CDC recommended using only edetate calcium disodium, not edetate disodium, to children because edetate disodium may induce tetany and possible hypocalcemia as illustrated in this case. The use of chelation therapy in autistic children has not been validated and can have tragic consequences. | 18,949,650 |
'Education? It is irrelevant to my job now. It makes me very depressed ...': exploring the health impacts of under/unemployment among highly skilled recent immigrants in Canada. | Immigrants account for 20% of the population and 60% of total population growth in Canada (Statistics Canada 2001). The majority of immigrants are accepted for entry to Canada under the Skilled Worker Program in order to fill employment shortages in the labour market (CIC 2007). Recent research has revealed that an increasing number of immigrants who gain entry under this programme face significant barriers to employment. As a result, many remain unemployed or accept employment outside of and below their field of education and training. However, the impacts such employment circumstances have on the health of immigrants have not yet been examined. This paper presents the results of a collaborative research project that explores the health impacts of under/unemployment among skilled immigrants in Mississauga, Ontario, Canada. In-depth interviews are used to examine the experiences of employment and perceptions of subsequent health impacts among 22 recent immigrants. The participants most frequently identified mental health impacts due to a lack of income, loss of employment-related skills, loss of social status and family pressures. These health concerns are also extended to family members. In addition to mental health, physical health is perceived to be affected by employment circumstances through high levels of stress and strenuous working conditions. These findings shed light on the nature of the links between employment and health relationship as well as determinants of immigrant health. Additional research is required to examine the long-term effects of under/unemployment. | 18,949,654 |
Playing with confidence: the relationship between imagery use and self-confidence and self-efficacy in youth soccer players. | Confidence has been one of the most consistent factors in distinguishing the successful from the unsuccessful athletes (Gould, Weiss, & Weinberg, 1981) and Bandura (1997) proposed that imagery is one way to enhance confidence. Therefore, the purpose of the present study was to examine the relationship between imagery use and confidence in soccer (football) players. The participants included 122 male and female soccer athletes ages 11-14 years participating in both house/ recreation (n = 72) and travel/competitive (n = 50) levels. Athletes completed three questionnaires; one measuring the frequency of imagery use, one assessing generalised self-confidence, and one assessing self-efficacy in soccer. A series of regression analyses found that Motivational General-Mastery (MG-M) imagery was a signifant predictor of self-confidence and self-efficacy in both recreational and competitive youth soccer players. More specifically, MG-M imagery accounted for between 40 and 57% of the variance for both self-confidence and self-efficacy with two other functions (MG-A and MS) contributing marginally in the self-confidence regression for recreational athletes. These findings suggest that if a youth athlete, regardless of competitive level, wants to increase his/her self-confidence or self-efficacy through the use of imagery, the MG-M function should be emphasised. | 18,949,659 |
Reduced expression and defective modulation of TNF receptor/ligand family molecules on proB-ALL blasts. | There is a subgroup of pediatric patients with an immature immunophenotype of proB-ALL that still poses a therapeutic challenge, even if the overall prognosis in B cell precursor acute lymphoblasic leukemia (BCP-ALL) is very good. Due to impaired treatment response these patients are prone to suffer relapse and are thus by definition stratified into the clinically defined high risk group receiving intensified chemotherapy. Besides response to chemotherapy long term prognosis is also influenced by immunological control mechanisms. Thus, high expression of the TNF receptor CD40 has been shown to prevent particularly late relapse in BCP-ALL suggesting a pivotal role of this regulatory molecule for maintenance of the remission status. We therefore determined the baseline expression and CD40-mediated modulation of TNF receptor and costimulatory molecules in 5 patients with proB-ALL, 8 with preB-ALL and 22 with c-ALL performing FACS analysis. We particularly compared the TNF receptor status on proB-ALL blasts to the expression on more mature preB- and c-ALL blasts. Here, we demonstrate for the first time a significantly lower baseline expression and CD40-induced modulation capacity of TNF receptor and costimulatory molecules in pediatric proB-ALL compared to more mature precursor B-ALL blasts. The lower expression and defective capacity of proB-ALL blasts to respond to CD40 ligand stimulation might resemble the immature feature of these blasts and besides increased chemoresistance contribute to the impaired prognosis of these patients due to escape from apoptosis and immunological control mechanisms. | 18,949,670 |
Impaired CD95-mediated apoptosis in autoimmunity and occurrence of a p22 Caspase-8 cleavage product in JIA. | Altered apoptosis can lead to autoimmune diseases such as systemic lupus erythematosus (SLE). Juvenile idiopathic arthritis (JIA) is another autoimmune disease characterized by autoinflammation. During this process activated T-cells accumulate in the synovial fluid. We hypothesized that resistance to CD95-mediated apoptosis could contribute to autoimmune phenotypes. We isolated highly activated T cells (CD45RO+ and CD95+) by magnetic separation from healthy controls, JIA patients and patients with other autoimmune diseases. In these purified cells, apoptosis was induced by stimulation with recombinant human soluble CD95 ligand (rhsCD95L) or dexamethasone and analyzed by flow cytometry. In addition, cleavage and expression of apoptosis mediators (Caspase-8 and -3) and regulators (FLIP, Bcl-2, Bcl-xL) were analyzed in mononuclear cells using immunoblot technique. Apoptosis upon CD95 stimulation, but not dexamethasone treatment, was reduced in JIA patients and patients with other autoimmune diseases compared to healthy controls. Additionally we observed a non-canonical cleavage pattern of Caspase-8 resulting in a p22 fragment and high expression of FLIP in SFMCs of patients with JIA. Expression and cleavage of proteins of the CD95 pathway is altered in JIA providing a possible explanation for resistance against death receptor-mediated apoptosis. Dexamethasone-induced apoptosis, however, is intact arguing against a general defect in apoptosis. The implications of the p22 fragment regarding apoptosis have to be further analyzed. The strong expression of FLIPShort in SFMCs may as well result from the highly activated status of the cells or be a feature of autoimmunity. | 18,949,671 |
In silico reconstruction of the amino acid metabolic pathways of Trypanosoma cruzi. | Trypanosoma cruzi is the epidemiological agent of Chagas' disease, affecting most of Central and South America, constituting a significant health and socio-economic problem. The parasite has a metabolism largely based on the consumption of amino acids, which participate in a diversity of metabolic pathways, leading to many crucial compounds for the survival of this parasite. Study of its enzymes has the potential to disclose new therapeutic targets and foster the development of new drugs. In this study, we employed computational approaches to reconstruct in silico the amino acid metabolic pathways of T. cruzi, aiming to link genomic information with functional information. For that, protein sequences from 570 EC classes belonging to 25 different pathways in general amino acid metabolism were downloaded from KEGG. A subset of 471 EC classes had at least one sequence deposited. Clustering of the proteins belonging to each EC class was performed using a similarity-based approach implemented in the tool AnEnPi. Reconstruction of the metabolic pathways comprising the amino acid metabolism of T. cruzi was performed by analyzing the output of BLASTP, using as query the dataset of predicted proteins of T. cruzi against all sequences of each individual cluster. This approach allowed us to identify 764 T. cruzi proteins probably involved in the metabolism of amino acids as well as the identification of several putative cases of analogy. Furthermore, we were able to identify several enzymatic activities of T. cruzi that were not previously included in KEGG. | 18,949,706 |
Continuous renal replacement therapy combined with extracorporeal membrane oxygenation in advanced cardiac failure patients. | Acute renal failure during extracorporeal membrane oxygenation (ECMO) support is associated with extremely high mortality. This report describes treatment of myocardial dysfunction in one 48-year-old and one 11-year-old patient. Venoarterial ECMO was required to support myocardial dysfunction. Continuous venovenous hemodialysis was performed for acute renal failure with pulmonary edema and oliguria. Both patients survived following treatment with venoarterial ECMO combined with continuous venovenous hemodialysis. | 18,949,736 |
Osteopontin expression according to molecular profile of invasive breast cancer: a clinicopathological and immunohistochemical study. | Osteopontin (OPN) is a secreted, calcium-binding phosphorylated glycoprotein involved in several physiological and pathological events such as angiogenesis, apoptosis, inflammation, wound healing, vascular remodeling, calcification of mineralized tissues, and induction of cell proteases. There is growing interest in the role of OPN in breast cancer. In an attempt to obtain new insight into the pathogenesis of OPN-associated breast carcinomas, an immunohistochemical panel with 17 primary antibodies including cytokeratins and key regulators of the cell cycle was performed in 100 formalin-fixed paraffin-embedded samples of invasive breast carcinomas. OPN was expressed in 65% of tumors and was negatively correlated with estrogen (p=0.0350) and progesterone (p=0.0069) receptors, but not with the other markers and clinicopathological features evaluated including age, menstrual status, pathological grading, tumor size, and metastasis. There was no correlation between OPN expression and carcinomas of the basal-like phenotype (p=0.1615); however, OPN correlated positively with c-erbB-2 status (p=0.0286) and negatively with carcinomas of the luminal subtype (p=0.0353). It is well known that carcinomas overexpressing c-erbB-2 protein have a worse prognosis than luminal tumors. Here, we hypothesize that the differential expression of OPN in the first subtype of carcinomas may contribute to their more aggressive behavior. | 18,949,741 |
Expression of periostin in patients with non-small cell lung cancer: correlation with angiogenesis and lymphangiogenesis. | The aim of this study was to evaluate periostin expression measured immunohistochemically in patients with non-small cell lung cancer (NSCLC) and to determine its association with clinical features, prognosis, angiogenesis, and lymphangiogenesis. We investigated periostin expression in a series of 88 patients with NSCLC. We also determined whether expression of periostin correlated with microvessel density and lymphatic microvessel density. Periostin was expressed in 42% of 88 patients. Its expression was significantly correlated with tumor size, lymph node metastasis, disease stage, and lymphatic invasion (p=0.0128, 0.0015, 0.0310 and 0.0273, respectively). There also was a significant relation between periostin expression and microvessel density and lymphatic microvessel density (all p<0.0001). Five-year survival rates were better in patients with negative periostin expression than in those with positive periostin expression (p=0.0044). Periostin expression was not significant in a multivariate additive model. Our findings show that periostin correlates with increased tumor progression and a worse prognosis in NSCLC, as well as with angiogenesis and lymphangiogenesis. | 18,949,745 |
Comparison of outcome measures from a trial of mycophenolate mofetil in myasthenia gravis. | We determined the strength of correlation among, and responsiveness of, outcome measures used in a multicenter, double-blind, placebo-controlled trial of mycophenolate mofetil in combination with prednisone in myasthenia gravis (MG). The primary efficacy measure was the change from baseline in the Quantitative MG (QMG) score at week 12. Secondary outcome measures included the MG-Activities of Daily Living profile (MG-ADL) and MG Manual Muscle Test (MMT). The measures were collected at baseline and at weeks 4, 8, and 12 in the blinded study and at weeks 16, 20, 28, and 36 in an optional open-label extension. At baseline, the QMG was moderately correlated with the MG-ADL (r=0.55, P<0.0001) and the MMT (r=0.53, P<0.0001), but the correlation between the MG-ADL and the MMT was lower (r=0.30, P=0.007). These findings were similar at weeks 4, 8, and 12. Similar correlations were found among the changes in scores from baseline at weeks 12 and 36. The MMT and MG-ADL appeared to be the most sensitive measures for changes in MG status at weeks 12 and 36. Although a task force has recommended use of the QMG in prospective MG trials, the MMT and MG-ADL appear to be suitable alternatives and offer potential advantages. No special training or equipment is required, and they take less time. | 18,949,779 |
A general synthesis for PEDOT-coated nonconductive materials and PEDOT hollow particles by aqueous chemical polymerization. | A method for coating functionalized poly(3,4-ethylenedioxythiophene) (PEDOT) on nonconductive substrates in aqueous solution allows the deposition of PEDOT thin layers on various substrates, including silica and polystyrene (PS) nanoparticles, siliceous mesocellular foam, and chitosan-alginate fibers. The surface property is tuned by controlling the monomer composition in the aqueous solutions. Using appropriate organic solvents to remove the PS cores of PEDOT-coated PS nanoparticles, hollow PEDOT particles with single holes and PEDOT capsules can be formed. | 18,949,792 |
Design of multicomponent microgels by selective deposition of nanomaterials. | In the present paper a method for the targeted deposition of different nanomaterials on aqueous microgels is described. In the first stage poly(3,4-ethylenedioxythiophene) (PEDOT) nanorods are introduced into the microgel structure by in situ oxidative polymerization. In the second stage hydrogen tetrachloroaurate is used to transform PEDOT chains to an oxidized state in the microgel structure, leading to the fixation of chloroaurate anions on the surface of the PEDOT nanorods. The reduction of chloroaurate ions induces the formation of gold nanoparticles (AuNPs) predominantly located on the PEDOT surface. Obtained microgel/PEDOT/AuNP hybrid particles with different nanoparticle loadings exhibit superior colloidal stability and temperature sensitivity. The microgel/PEDOT/AuNP hybrid microgels exhibit extraordinary catalytic activity in aqueous media. | 18,949,794 |
Synthetic polymers in the marine environment: a rapidly increasing, long-term threat. | Synthetic polymers, commonly known as plastics, have been entering the marine environment in quantities paralleling their level of production over the last half century. However, in the last two decades of the 20th Century, the deposition rate accelerated past the rate of production, and plastics are now one of the most common and persistent pollutants in ocean waters and beaches worldwide. Thirty years ago the prevailing attitude of the plastic industry was that "plastic litter is a very small proportion of all litter and causes no harm to the environment except as an eyesore" [Derraik, J.G.B., 2002. The pollution of the marine environment by plastic debris: a review. Mar. Pollut. Bull. 44(9), 842-852]. Between 1960 and 2000, the world production of plastic resins increased 25-fold, while recovery of the material remained below 5%. Between 1970 and 2003, plastics became the fastest growing segment of the US municipal waste stream, increasing nine-fold, and marine litter is now 60-80% plastic, reaching 90-95% in some areas. While undoubtedly still an eyesore, plastic debris today is having significant harmful effects on marine biota. Albatross, fulmars, shearwaters and petrels mistake floating plastics for food, and many individuals of these species are affected; in fact, 44% of all seabird species are known to ingest plastic. Sea turtles ingest plastic bags, fishing line and other plastics, as do 26 species of cetaceans. In all, 267 species of marine organisms worldwide are known to have been affected by plastic debris, a number that will increase as smaller organisms are assessed. The number of fish, birds, and mammals that succumb each year to derelict fishing nets and lines in which they become entangled cannot be reliably known; but estimates are in the millions. We divide marine plastic debris into two categories: macro, >5 mm and micro, <5 mm. While macro-debris may sometimes be traced to its origin by object identification or markings, micro-debris, consisting of particles of two main varieties, (1) fragments broken from larger objects, and (2) resin pellets and powders, the basic thermoplastic industry feedstocks, are difficult to trace. Ingestion of plastic micro-debris by filter feeders at the base of the food web is known to occur, but has not been quantified. Ingestion of degraded plastic pellets and fragments raises toxicity concerns, since plastics are known to adsorb hydrophobic pollutants. The potential bioavailability of compounds added to plastics at the time of manufacture, as well as those adsorbed from the environment are complex issues that merit more widespread investigation. The physiological effects of any bioavailable compounds desorbed from plastics by marine biota are being directly investigated, since it was found 20 years ago that the mass of ingested plastic in Great Shearwaters was positively correlated with PCBs in their fat and eggs. Colonization of plastic marine debris by sessile organisms provides a vector for transport of alien species in the ocean environment and may threaten marine biodiversity. There is also potential danger to marine ecosystems from the accumulation of plastic debris on the sea floor. The accumulation of such debris can inhibit gas exchange between the overlying waters and the pore waters of the sediments, and disrupt or smother inhabitants of the benthos. The extent of this problem and its effects have recently begun to be investigated. A little more than half of all thermoplastics will sink in seawater. | 18,949,831 |
Mechanisms of action of phthalate esters, individually and in combination, to induce abnormal reproductive development in male laboratory rats. | Phthalate esters are high production volume chemicals used to impart flexibility to polyvinyl chloride products as well as other applications. In the male laboratory rat, the period of sexual differentiation in utero is particularly sensitive to certain phthalate esters, which induce a suite of reproductive malformations, including epididymal and gubernacular agenesis. The fetal rat testes are a main target for phthalate esters as evidenced by a reduction in testosterone production and insulin-like hormone 3 (insl3) expression, a peptide hormone critical for testis descent. Histopathology of fetal and postnatal testes reveals that in utero exposure to phthalate esters disrupts Leydig and Sertoli cell maturation leading to a reduction in germ cells in the malformed seminiferous tubules in adulthood as well as an increased incidence of multinucleated germ cells. There are some strain-specific differences in the target organs in the male reproductive tract in rats affected by phthalate esters. Mixtures of phthalate esters with one another and with other anti-androgenic compounds exhibit cumulative, largely dose-additive effects on male reproductive tract development when administered during sexual differentiation in utero. Since phthalate ester metabolites are detected in maternal and fetal body fluids, and androgen-signaling and insl3 are highly conserved among mammals, phthalates may potentially affect human reproductive development. | 18,949,836 |
Comparative analysis of protein profiles of wild virulent (E156) and aroA-htrA double deletion mutant vaccine strain (S30) of Salmonella enterica subsp. enterica serovar Abortusequi under in vivo and in vitro growth conditions. | In the present study, cell lysate and cell supernatant of the both strains i.e., virulent wild type (E156) and mutant (S30) vaccine strains of Salmonella enterica subspecies enterica serovar Abortusequi (S. Abortusequi), grown under varied in vivo and in vitro conditions were subjected to SDS PAGE and western blotting (using rabbit hyperimmune serum). Variation in growth conditions did not have any significant effect on expression of different proteins. SDS PAGE of E156 and S30 cell lysate (CL) revealed 26 and 28 bands, respectively with 3 prominent proteins of 71, 46 and 42 kDa in cell lysate of E 156 and 4 prominent proteins 71, 65, 46 and 40 kDa in S30 strain. The cell supernatant (CS) from both the strains, subjected to SDS PAGE, exhibited similarity in protein profile among these strains, however three bands of 65, 53 and 40 kDa were more prominent in CS preparation of S30, whereas a 56 kDa protein was prominent in CS of E156. Western blotting of E156 and S30 revealed 3 unique proteins of 65, 53 and 40 kDa present in CS preparation of S30 strains which could be used for differentiation of mutant and wild strains and also in development of test for differentiating vaccinated animals from naturally infected. | 18,949,890 |
A case report of hemangioendothelioma of the hard palate. | Hemangioendothelioma is a rare vascular tumour with potential for malignancy that is intermediate between that of a benign hemangioma and a malignant angiosarcoma. This tumour occurs infrequently in the head and neck regions. In this report, we describe and discuss a case of hemangioendothelioma that originated in the hard palate of a 49-year-old woman. | 18,949,965 |
Cochlear implantation in 3 adults with auditory neuropathy/auditory dys-synchrony. | We describe 3 adult patients with auditory neuropathy/auditory dys-synchrony (AN/AD) who underwent cochlear implantation. All patients had absent or poorly formed auditory brainstem responses (ABRs) in combination with preserved otoacoustic emissions (OAEs). They exhibited various aetiologies and a large variation in clinical features known to be consistent with AN/AD. Cochlear implantation was successful in 2 out of 3 cases. We conclude that AN/AD implantee candidates should be counselled with care. | 18,949,967 |
[Chronic urticaria: which evaluation? Which management?]. | Chronic urticaria (CU) is an inflammatory skin disease characterized by the recurrence of transient and itching maculopapular skin lesions for more than 6 weeks. Clinical diagnosis is easy but eliciting factors are rarely evidenced. Recently, autoimmune mechanisms have been recognized as a cause of CU. Carefully history and physical examination are the most important elements of the etiological diagnosis. Exhausted tests are expensive and their cost-effectiveness is low. In the vast majority of cases this disease is benign but the quality of life can be severely affected. Second generation non-sedating antihistamines are the cornerstone of the treatment. | 18,949,996 |
[Peri-uvulopalatopharyngoplasty erythrocyte immune function analysis in patients with obstructive sleep apnea hypopnea syndrome]. | To investigate the effect of ECR I, RBC-C3bRR, RBC-ICR on obstructive sleep apnea-hypopnea syndrome (OSAHS). Fifty-four inpatients with OSAHS and 20 healthy controls at the same age were enrolled. 1 ml fresh whole blood with stomach empty in early morning were collected before and after the surgery to detect ECR I , RBC-C3bRR and RBC-ICR. The erythrocyte immune function of the OSAHS group was lower than that of the control group. Erythrocyte immune functional disorder plays an important role in OSAHS and surgical procedures is effective in correcting the changes. | 18,950,003 |
[Four-stage gradual expanding approach of problem based learning in otorhinolaryngology]. | The aim of the study is to cover the shortages of PBL, such as time-consuming, abstract, lacking of the course of clinic practice, and to introduce PBL to the teaching of otorhinolaryngology. By the improvement of the international classic teaching model of PBL, we put forward "four-stage gradual expanding approach of PBL" and establish "four-stage gradual expanding approach of PBL in otorhinolaryngology". Through the four stages of watching PBL, simulation PBL, internship PBL, practice PBL, we have accomplished the organic integration of theory teaching and clinical practice. This teaching method is more adaptive to the teaching of otorhinolaryngology, and it can help the medicine students to establish the whole concept of medicine and can stimulate them to form the good habits of self-regulated learning and life-long learning efficiently. | 18,950,012 |
[Establishment of the database of the 3D facial models for the plastic surgery based on network]. | To collect the three-dimensional (3D) facial data of 30 facial deformity patients by the 3D scanner and establish a professional database based on Internet. It can be helpful for the clinical intervention. The primitive point data of face topography were collected by the 3D scanner. Then the 3D point cloud was edited by reverse engineering software to reconstruct the 3D model of the face. The database system was divided into three parts, including basic information, disease information and surgery information. The programming language of the web system is Java. The linkages between every table of the database are credibility. The query operation and the data mining are convenient. The users can visit the database via the Internet and use the image analysis system to observe the 3D facial models interactively. In this paper we presented a database and a web system adapt to the plastic surgery of human face. It can be used both in clinic and in basic research. | 18,950,030 |
Physiological time model for predicting adult emergence of western corn rootworm (Coleoptera: Chrysomelidae) in the Texas High Plains. | Field observations at three locations in the Texas High Plains were used to develop and validate a degree-day phenology model to predict the onset and proportional emergence of adult Diabrotica virgifera virgifera LeConte (Coleoptera: Chrysomelidae) adults. Climatic data from the Texas High Plains Potential Evapotranspiration network were used with records of cumulative proportional adult emergence to determine the functional lower developmental temperature, optimum starting date, and the sum of degree-days for phenological events from onset to 99% adult emergence. The model base temperature, 10 degrees C (50 degrees F), corresponds closely to known physiological lower limits for development. The model uses a modified Gompertz equation, y = 96.5 x exp (-(exp(6.0 - 0.00404 x (x - 4.0), where x is cumulative heat (degree-days), to predict y, cumulative proportional emergence expressed as a percentage. The model starts degree-day accumulation on the date of corn, Zea mays L., emergence, and predictions correspond closely to corn phenological stages from tasseling to black layer development. Validation shows the model predicts cumulative proportional adult emergence within a satisfactory interval of 4.5 d. The model is flexible enough to accommodate early planting, late emergence, and the effects of drought and heat stress. The model provides corn producers ample lead time to anticipate and implement adult control practices. | 18,950,040 |
Progression of ash canopy thinning and dieback outward from the initial infestation of emerald ash borer (Coleoptera: Buprestidae) in southeastern Michigan. | Our objective was to characterize the rate at which ash (Fraxinus spp.) trees decline in areas adjacent to the leading edge of visible ash canopy thinning due to emerald ash borer, Agrilus planipennis Fairmaire (Coleoptera: Buprestidae). Trees in southeastern Michigan were surveyed from 2003 to 2006 for canopy thinning and dieback by comparing survey trees with a set of 11 standard photographs. Freeways stemming from Detroit in all directions were used as survey transects. Between 750 and 1,100 trees were surveyed each year. A rapid method of sampling populations of emerald ash borer was developed by counting emerald ash borer emergence holes with binoculars and then felling trees to validate binocular counts. Approximately 25% of the trees surveyed for canopy thinning in 2005 and 2006 also were sampled for emerald ash borer emergence holes using binoculars. Regression analysis indicates that 41-53% of the variation in ash canopy thinning can be explained by the number of emerald ash borer emergence holes per tree. Emerald ash borer emergence holes were found at every site where ash canopy thinning averaged > 40%. In 2003, ash canopy thinning averaged 40% at a distance of 19.3 km from the epicenter of the emerald ash borer infestation in Canton. By 2006, the point at which ash trees averaged 40% canopy thinning had increased to a distance of 51.2 km away from Canton. Therefore, the point at which ash trees averaged 40% canopy thinning, a state of decline clearly visible to the average person, moved outward at a rate of 10.6 km/yr during this period. | 18,950,047 |
Impact of production system on development of insecticide resistance in Frankliniella occidentalis (Thysanoptera: Thripidae). | The western flower thrips, Frankliniella occidentalis (Pergande) (Thysanoptera: Thripidae), has become one of the most difficult insects to control in the intensive agriculture of southeastern Spain. However, resistance problems are quite different in two neighboring areas, Murcia and Almeria, with distinct production systems. Thirty-six field populations of western flower thrips from sweet pepper crops were collected in two different dates in Murcia and Almeria in 2005 and 2006. Western flower thrips populations collected were exposed to a diagnostic concentration of spinosad, methiocarb, acrinathrin, and formetanate. The results allowed the recognition of higher levels of resistance in Almeria compared with Murcia throughout the growing season. The mortality at the diagnostic concentration for spinosad (120 ppm) in western flower thrips populations ranged from 34 to 81% in Almeria, and from 73 to 100% in Murcia. The mortalities at the diagnostic concentration to acrinathrin (800 ppm) and formetanate (8000 ppm) were 17-31% in Almeria and 77-100% in Murcia, and 14-41% in Almeria and 48-99% in Murcia, respectively, indicating large geographic variations. Toxicity of methiocarb was higher for western flower thrips populations from both areas. However, mortality at the diagnostic concentration of methiocarb (2000 ppm) varied from 56 to 90% in Almeria, and it was from 94 to 100% in Murcia. The impact of production systems and agricultural practices of each area on the development and stability of insecticide resistance is discussed. | 18,950,052 |
Linkage between one of the polygenic hexythiazox resistance genes and an etoxazole resistance gene in the twospotted spider mite (Acari: Tetranychidae). | Genetic linkage between hexythiazox and etoxazole resistance loci was analyzed by crossing experiments. Two strains, one resistant (R) and the other susceptible (S) to both chemicals were established from field-collected Tetranychus urticae Koch (Acari: Tetranychidae) populations that were further selected in the laboratory. To analyze the recombination rate of the loci associated with resistance, we tested the ovicidal effects of a mixed solution of hexythiazox and etoxazole on haploid F2 eggs laid by F1 females from an R female x S male cross. This revealed tight or complete linkage between the hexythiazox and etoxazole resistance loci. We then assessed the number of loci associated with resistance to each acaricide based on mortality in the haploid F3 progeny (eggs) of F2 females from an F1 female (R x S) x S male testcross. The mortality rate indicated that etoxazole resistance was largely controlled by a single major locus, whereas hexythiazox resistance was controlled by more than one locus. Thus, one hexythiazox resistance locus was tightly or completely linked to the etoxazole resistance locus. | 18,950,055 |
Expansive or limitative strategy? A case study of organisational responses to new public health. | Since the emergence of new public health in the 1970s, health has not merely been considered the absence of disease, but physical, mental and social wellbeing. This article seeks to analyzes the implications of this broad concept of health at an organizational level. The paper presents a qualitative case study of boundary drawing in a Danish municipal agency in charge of planning and conducting health promoting and disease preventing activities from 1989 to 2005. The theoretical framework draws on Niklas Luhmann's organization theory. Two different organizational answers were found to the challenges inherent in the broad concept of new public health. First, the organization tried to increase its size and incorporate as many aspects of the environment as possible. This expansive strategy jeopardised the identity of the organization. Second, the organization tried to keep clear and tight boundaries and from this position irritate entities in the environment. This limitative strategy made the organization spend relatively more energy on organizing and controlling itself than on public health work. The case study shows how a broad concept of health makes boundary management topical in organizations dealing with health promotion and disease prevention. Organizations in charge of public health activities need to reflect on how they can create intelligent compensations for the disadvantages involved in an expansive or a limitative strategy. The broad concept of health inherent in new public health has been widely accepted and yet its challenges to organizational boundary drawing have attracted little attention. This paper provides an analysis of these challenges. | 18,950,074 |
Spectroscopic units in conjugated polymers: a quantum chemically founded concept? | In conjugated polymers the concept of spectroscopic units belonging to different spatial segments of the chain, which are responsible for the spectroscopic properties of the polymer, has been used to explain the spectral heterogeneity and the excitation migration by (Förster type) hopping transfer. In the present work we study the possible mechanism of segmentation of polythiophene into spectroscopic units by using quantum-chemical methods (ZINDO). We found that static geometric defects such as kinks or torsions do not result in a significant localization of the excited states to a certain segment. Hence, we propose that a dynamic localization of excitation due to the interaction between the nuclear and electronic degrees of freedom is responsible for the formation of the spectroscopic units. | 18,950,096 |
The Effect of a Magnetic Field on a RAPET (Reaction under Autogenic Pressure at Elevated Temperature) of MoO(OMe)(4): Fabrication of MoO(2) Nanoparticles Coated with Carbon or Separated MoO(2) and Carbon Particles. | In this article, we present results of the RAPET dissociation of MoO(OMe)4 at 700 degrees C in a closed Swagelok cell. The reaction produces molybdenum dioxide nanoparticles (20 nm) coated with carbon (20 nm). We have also carried out the same reaction under an applied magnetic field of 10 T. This reaction yielded different products. It produces a mixture of comparatively larger (50 nm) molybdenum dioxide nanoparticles and separated uncoated carbon particles (20-30 nm). | 18,950,118 |
A Density Functional Theory Study on the Effect of Ge Alloying on Hydrogen Desorption from SiGe Alloy Surfaces. | We have used density functional theory to investigate hydrogen desorption from SiGe alloy surfaces, and the effect of Ge alloying on the kinetics of hydrogen desorption via the prepairing and interdimer mechanisms. We find that the calculated activation barriers of the prepairing mechanism are affected by the surface atom bonded to the desorbing hydrogen atoms. On the other hand, our calculations show that the activation barrier for hydrogen desorption via the 2H interdimer mechanism is affected by all four surface atoms of the two neighboring dimers. For the 4H interdimer mechanism, we have shown that the activation barrier for hydrogen desorption is not significantly higher than the endothermicity of hydrogen desorption. We also find that the calculated activation barriers of the interdimer mechanisms are generally lower than those of the prepairing mechanism. In addition, our calculations show that surface Ge atoms on neighboring dimers on SiGe alloy surfaces have a minor effect on the calculated activation barriers of both the prepairing and interdimer mechanisms, which indicates that the effect of Ge alloying on hydrogen desorption is local in nature. We also discuss the effects of cluster size and constraints on the calculated reaction energies and activation barriers of hydrogen desorption via the two mechanisms. | 18,950,120 |
Combining optical trapping and single-molecule fluorescence spectroscopy: enhanced photobleaching of fluorophores. | To obtain high-resolution information on position or conformation of a molecule and at the same time apply forces to it, one can combine optical trapping with single-molecule fluorescence microscopy. The technical challenge in such an experiment is to discriminate a minute fluorescence signal from the much larger background signals caused by the trap and the fluorescence excitation laser light. We show here that this is feasible even when the fluorophore is directly attached to the trapped particle, by using optimized optical filters. We found, however, that the photostability of the fluorophores we tested suffered from the presence of the additional laser light used for trapping. We found that bleaching rates increased linearly with both the intensity of the trapping laser and the intensity of the fluorescence excitation light. Photobleaching rates were unaffected by the presence or absence of oxygen, but were significantly diminished in the presence of antioxidants. Our results indicate that the enhanced photobleaching is caused by the absorption of a visible photon followed by the excited-state absorption of a near-infrared photon. The higher excited singlet states generated in this way readily form nonfluorescent dye cations. We found that different dyes suffer to a different extent from the excited-state absorption, with Cy3 being worst and tetramethylrhodamine least affected. | 18,950,137 |
Inertial effects on the intramolecular vibrational energy redistribution and nonadiabatic photoisomerization of a 2,3-substituted 1,3-butadiene: a quasi-classical CASSCF dynamics study. | Quasi-classical CASSCF trajectory calculations have been carried out on s-cis-1,3-butadiene and substituted 2,3-dideuterio-1,3-butadiene (DDB) to assess the inertial effect on the ultrafast nonadiabatic deactivation of their first singlet excited states. Calculations indicate that even this modest increase in the mass of the 2,3-substituents noticeably affects the photodynamics of cis --> trans isomerization, by reducing the efficiency of the vibrational energy leakage between the initial relaxation and subsequent nonadiabatic decay modes. In qualitative agreement with experimental findings on related 1,3-dienes, the slowing down of the intramolecular vibrational energy redistribution (IVR) upon substitution results in extended excited-state lifetimes and reorients the photoregioselectivity toward cis rotamers and cyclic products. | 18,950,146 |
1,3-Dipolar cycloaddition of organic azides to alkynes by a dicopper-substituted silicotungstate. | The dicopper-substituted gamma-Keggin silicotungstate TBA 4[gamma-H2SiW10O36Cu2(mu-1,1-N3)2] (I, TBA = tetra- n-butylammonium) could act as an efficient precatalyst for the regioselective 1,3-dipolar cycloaddition of organic azides to alkynes. Various combinations of substrates (four azides and eight alkynes) were efficiently converted to the corresponding 1,2,3-triazole derivatives in excellent yields without any additives. The present system was applicable to a larger-scale cycloaddition of benzyl azide to phenylacetylene under solvent-free conditions (100 mmol scale) in which 21.5 g of the analytically pure corresponding triazole could be isolated. In this case, the turnover frequency and the turnover number reached up to 14,800 h(-1) and 91,500, respectively, and these values were the highest among those reported for the copper-mediated systems so far. In addition, I could be applied to the one-pot synthesis of 1-benzyl-4-phenyl-1H-1,2,3-triazole from benzyl chloride, sodium azide, and phenylacetylene. The catalyst effect, kinetic, mechanistic, and computational studies show that the reduced dicopper core plays an important role in the present 1,3-dipolar cycloaddition. | 18,950,175 |
Once cleaved C-C bond was reformed: reversible C-C bond cleavage of dihydroindenyltitanium complexes. | The once cleaved carbon-carbon bond of the Cp moiety in 2 was recombined in indene products. Aslo, we propose a novel mechanism for the cleavage of the carbon-carbon bond of the Cp moiety. | 18,950,176 |
Effect of beer/red wine marinades on the formation of heterocyclic aromatic amines in pan-fried beef. | The effect of beer or red wine marinades on the reduction of heterocyclic aromatic amines (HAs) formation in pan-fried beef was compared. The cooking experiments were performed under well-controlled temperature and time conditions. The samples were analyzed for HAs contents using solid-phase extraction and high-performance liquid chromatography-diode array detection/fluorescence detection. Unmarinated samples cooked in similar conditions provided reference HAs levels. Marinating with beer or with red wine resulted in decreased levels of HAs. The amount of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline reduced significantly, respectively, around 88 and 40% after 6 h of marinating with beer or with wine. High variations were observed for reductions of AalphaC, ranging between 7 and 77%. Only beer marinade significantly reduced the levels of 4,8-DiMeIQx at 1, 2, and 4 h of marinating. Multivariate statistical treatment of results indicated that beer can be more efficient on the reduction of some HAs formation. In addition, results from descriptive sensory analysis of unmarinated and 2 h marinated beef samples, tested for by two trained sensory panels, pointed to beer marinade as the most adequate for maintaining the usual overall appearance and quality of the pan-fried steaks. | 18,950,185 |
Internal sodium ions and water molecules in guanine quadruplexes: magnetic relaxation dispersion studies of [d(G3T4G3)]2 and [d(G4T4G4)]2. | The structural stability of guanine quadruplexes depends critically on an unusual configuration of dehydrated Na (+) or K (+) ions, closely spaced along the central axis of the quadruplex. Crystallography and NMR spectroscopy indicate that these internal ions can be located between the G-quartet planes as well as in the thymine loops, but the precise ion coordination has been firmly established in only a few cases. Here, we examine the bimolecular diagonal-looped foldback quadruplexes [d(G 3T 4G 3)] 2 (Q3) and [d(G 4T 4G 4)] 2 (Q4) by (2)H, (17)O, and (23)Na magnetic relaxation dispersion (MRD). The MRD data indicate that both quadruplexes contain Na (+) ions between the T 4 loops and the terminal G-quartets and that these ions have one water ligand. These ions exchange with external ions on a time scale of 10-60 mus at 27 degrees C, while their highly ordered water ligands have residence times in the range 10 (-8)-10 (-6) s. The MRD data indicate that Q4 contains three Na (+) ions in the stem sites, in agreement with previous solid-state (23)Na NMR findings but contrary to the only crystal structure of this quadruplex. For Q3, the MRD data suggest a less symmetric coordination of the two stem ions. In both quadruplexes, the stem ions have residence times of 0.6-1.0 ms at 27 degrees C. The equilibrium constant for Na (+) --> K (+) exchange is approximately 4 for both loop and stem sites in Q3, in agreement with previous (1)H NMR findings. | 18,950,191 |
Importance of direct interactions with lipids for the function of the mechanosensitive channel MscL. | We have studied the effects of lipid structure on the function of the mechanosensitive channel of large conductance (MscL) from Escherichia coli to determine whether effects follow from direct interaction between the lipids and protein or whether they follow indirectly from changes in the curvature stress in the membrane. The G22C mutant of MscL was reconstituted into sealed vesicles containing the fluorescent molecule calcein, and the release of calcein from the vesicles was measured following opening of the channel by reaction with [2-(triethylammonium)ethyl] methanethiosulfonate (MTSET), which introduces five positive charges into the region of the pore constriction. The presence of anionic lipids in the vesicle membrane changed the rates and amplitudes of calcein release, the effects not correlating with calculated changes in lipid spontaneous curvature. Mutation of charged residues in the Arg-104, Lys-105, Lys-106 cluster removed high-affinity binding of anionic lipids to MscL, and the presence of anionic lipid no longer affected calcein flux through MscL. Changing the zwitterionic lipid from phosphatidylcholine to phosphatidylethanolamine resulted in a large decrease in the rate of calcein release, the change in rate varying linearly with lipid composition, as expected if spontaneous curvature affected the rate of release. However, rates of release of calcein measured in the presence of phosphatidylethanolamine- N-methyl and phosphatidylethanolamine- N, N-dimethyl did not fit the correlation between rate and curvature established for the phosphatidylcholine/phosphatidylethanolamine mixtures. Rather, the effects of zwitterionic lipid headgroup on calcein flux suggested that what was important was the presence of a proton in the headgroup, able to take part in hydrogen bonding to MscL. We conclude that the function of MscL is likely to be modulated by direct interaction with the surrounding, annular phospholipids that contact the protein in the membrane. | 18,950,196 |
Au-Ag template stripped pattern for scanning probe investigations of DNA arrays produced by dip pen nanolithography. | We report on DNA arrays produced by dip pen nanolithography (DPN) on a novel Au-Ag micropatterned template stripped surface. DNA arrays have been investigated by atomic force microscopy (AFM) and scanning tunneling microscopy (STM) showing that the patterned template stripped substrate enables easy retrieval of the DPN-functionalized zone with a standard optical microscope permitting multi-instrument and multitechnique local detection and analysis. Moreover the smooth surface of the Au squares ( approximately 5-10 A roughness) allows AFM/STM to be sensitive to the hybridization of the oligonucleotide array with label-free target DNA. Our Au-Ag substrates, combining the retrieving capabilities of the patterned surface with the smoothness of the template stripped technique, are candidates for the investigation of DPN nanostructures and for the development of label-free detection methods for DNA nanoarrays based on the use of scanning probes. | 18,950,214 |
Chitosan-modified poly(acrylonitrile-co-acrylic acid) nanofibrous membranes for the immobilization of concanavalin A. | Lectin affinity membranes have been receiving much attention for the separation and detection of various glycoconjugates. In this work, we present a simple and efficient method for the preparation of lectin affinity nanofibrous membranes. Chitosan-modified poly(acrylonitrile-co-acrylic acid) (PANCAA) nanofibrous membranes were first prepared by a coupling reaction between the primary amino groups of chitosan and the carboxyl groups of PANCAA electrospun membranes. Surface characterizations by attenuated total reflectance Fourier transform infrared spectroscopy (FT-IR/ATR), X-ray photoelectron spectroscopy (XPS) and field-emission scanning electron microscopy (FESEM) confirm the chemical and morphological changes of the studied nanofibrous membranes. Fluorescence-labeled concanavalin A (FL-Con A) was then immobilized on these membranes via noncovalent binding. Analyses by fluorescence spectrophotometer (FS) and confocal laser scanning microscopy (CLSM) reveal that the immobilization of Con A onto the modified nanofibrous membranes has been successfully achieved on the basis of the electrostatic interaction and the specific recognition between Con A and chitosan. The results show that the amount of adsorbed FL-Con A increases dramatically with the increasing coupling degree of chitosan (CDC) on the nanofibrous membrane. Moreover, Con A immobilized on the chitosan-modified nanofibrous membranes (CMNMs) can remain relatively stable at pH 5.3. Therefore, it is believed that this work may provide a new kind of material for affinity application. | 18,950,224 |
Low-temperature control of nanoscale morphology for high performance polymer photovoltaics. | Understanding and controlling nanoscale morphology is crucial to the performance of polymer bulk heterojunction solar cells, as well as other optoelectronic devices such as polymer light-emitting diodes, field-effect transistors, and sensors. In photovoltaic devices, optimum blend morphologies must be commensurate with the nanometer length scales of exciton diffusion and charge separation. We report on a generally applicable method of optimizing the phase segregation in polymer-polymer bulk heterojunctions based on tuning mixtures of low and high boiling point solvents. We have characterized the resulting blend morphologies with nanometer resolution using a transient absorption technique that probes the distribution of paths traveled by the excitons themselves prior to generating charges at an interface. Photovoltaic efficiencies are accounted for in terms of exciton diffusion, geminate pair separation, and polymer ordering, all of which are sensitive to the nanoscale morphology determined by the composition of the solvent mixture. | 18,950,237 |
Clinical applications of urinary organic acids. Part I: Detoxification markers. | Modern instrumentation allows the measurement of organic acids in urine in their physiological concentration ranges. Eight of the compounds that are reported can serve as markers for specific toxicant exposure or detoxification challenges. Xylene exposure causes elevation of 2-methylhippurate, and orotic acid elevation reveals ammonia challenge that exceeds the capacity of the urea cycle. General hepatic detoxification stimulation by natural compounds, drugs, or xenobiotic compounds causes elevated levels of glucaric acid. Abnormalities of alpha-hydroxybutyrate, pyroglutamate, and sulfate can indicate up-regulated glutathione biosynthesis, impaired reformation of glutathione in the gamma-glutamyl cycle, and depleted total body glutathione status, respectively. Patterns of these compounds measured in a simple overnight urine specimen help to identify focal areas of clinical concern and monitor patient responses to detoxification interventions. | 18,950,247 |
The methylation, neurotransmitter, and antioxidant connections between folate and depression. | Depression is common - one-fourth of the U.S. population will have a depressive episode sometime in life. Folate deficiency is also relatively common in depressed people, with approximately one-third of depressed individuals having an outright deficiency. Folate is a water-soluble B-vitamin necessary for the proper biosynthesis of the monoamine neurotransmitters serotonin, epinephrine, and dopamine. The active metabolite of folate, 5-methyltetrahydrofolate (5-MTHF, L-methylfolate), participates in re-methylation of the amino acid metabolite homocysteine, creating methionine. S-adenosylmethionine (SAMe), the downstream metabolite of methionine, is involved in numerous biochemical methyl donation reactions, including reactions forming monoamine neurotransmitters. Without the participation of 5-MTHF in this process, SAMe and neurotransmitter levels decrease in the cerebrospinal fluid, contributing to the disease process of depression. SAMe supplementation was shown to improve depressive symptoms. 5-MTHF also appears to stabilize, enhance production of, or possibly act as a substitute for, tetrahydrobiopterin (BH4), an essential cofactor in monoamine neurotransmitter biosynthesis. There are few intervention studies of folic acid or 5-MTHF as a stand-alone treatment for depression related to folate deficiency; however, the studies that have been conducted are promising. Depressed individuals with low serum folate also tend to not respond well to selective serotonin reuptake inhibitor (SSRI) antidepressant drugs. Correcting the insufficiency by dosing folate along with the SSRI results in a significantly better antidepressant response. | 18,950,248 |
Alginate modification improves long-term survival and function of transplanted encapsulated islets. | Despite recent successes in islet transplantation, current immunosuppression protocols required to prevent graft rejection are not suitable for all patients. As a consequence, microencapsulation of islets in alginate has been proposed to protect islets from immune-mediated destruction. Success has been limited, however, due largely to problems with alginate biocompatibility and insufficient immunoprotection by the capsule. The aim of this study was to develop a purified, highly biocompatible, and highly stable alginate from commercially available alginate. We analyzed the chemical properties of the alginate before and after purification and compared in vivo survival and metabolic function of mouse islets encapsulated with either alginate in syngeneic recipients. Recipients of purified alginate capsules exhibited a 105-day graft survival rate of 90.5%, versus 69.2% for recipients of nonpurified alginate, with recipients of purified alginate capsules also showing improved nonfasting blood glucose levels and oral glucose challenges over recipients of nonpurified alginate. On recovery, islets encapsulated in purified alginate capsules demonstrated dramatically reduced capsular overgrowth, and an insulin secretory activity far superior to that of islets in nonpurified alginate capsules. We conclude from this study that alginate purification improves the survival and metabolic function of encapsulated islets. To our knowledge, this is the first paper using pre- and postmodification alginate to demonstrate the direct benefit of purification on transplantation success of islets in simple, open-pore capsules. | 18,950,258 |
Vision salvage after resection of a giant meningioma in a patient with a loss in light perception. | Clinical approaches to the surgical management of optic chiasm compression stress quick action, as several case series have demonstrated minimal vision restoration following aggressive decompression in patients presenting more than 3 days after the onset of blindness. The authors here report the case of a 48-year-old woman who presented with near-complete binocular vision loss but regained visual function following surgical removal of a giant planum-tuberculum meningioma, which was performed 8 days after a documented loss in light perception. The interval between the patient's vision loss and successful vision-restoring decompressive surgery is the longest recorded to date in the literature. This case shows the importance of aggressive decompression of mass lesions despite extended intervals of optic nerve dysfunction. | 18,950,266 |
Chondrogenic differentiation of adipose-derived adult stem cells by a porous scaffold derived from native articular cartilage extracellular matrix. | Adipose-derived adult stem cells (ASCs) have the ability to differentiate into a chondrogenic phenotype in response to specific environmental signals such as growth factors or artificial biomaterial scaffolds. In this study, we examined the hypothesis that a porous scaffold derived exclusively from articular cartilage can induce chondrogenesis of ASCs. Human ASCs were seeded on porous scaffolds derived from adult porcine articular cartilage and cultured in standard medium without exogenous growth factors. Chondrogenesis of ASCs seeded within the scaffold was evident by quantitative RT-PCR analysis for cartilage-specific extracellular matrix (ECM) genes. Histological and immunohistochemical examination showed abundant production of cartilage-specific ECM components-particularly, type II collagen-after 4 or 6 weeks of culture. After 6 weeks of culture, the cellular morphology in the ASC-seeded constructs resembled those in native articular cartilage tissue, with rounded cells residing in the glycosaminoglycan-rich regions of the scaffolds. Biphasic mechanical testing showed that the aggregate modulus of the ASC-seeded constructs increased over time, reaching 150 kPa by day 42, more than threefold higher than that of the unseeded controls. These results suggest that a porous scaffold derived from articular cartilage has the ability to induce chondrogenic differentiation of ASCs without exogenous growth factors, with significant synthesis and accumulation of ECM macromolecules, and the development of mechanical properties approaching those of native cartilage. These findings support the potential for a processed cartilage ECM as a biomaterial scaffold for cartilage tissue engineering. Additional in vivo evaluation is necessary to fully recognize the clinical implication of these observations. | 18,950,290 |
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