title stringlengths 0 1.13k | abstract stringlengths 1 15.7k | PMID int64 22 36.5M |
|---|---|---|
Chromosome 9p21.3 is associated with early-onset coronary heart disease in the Irish population. | Coronary heart disease (CHD) remains a leading cause of death across the world. A region on chromosome 9p21.3 has been recently reported to be associated with CHD. We evaluated 3 SNPs and 3 common haplotypes in the 9p21.3 region in 1494 individuals from 580 Irish families, where at least 1 member had early-onset (males <or=55 yr, females <or=60 yr) CHD. Genotypes were determined by multiplex SNaPshot technology. Using the combined TDT/S-TDT test, the 3 single nucleotide polymorphisms (SNP), rs10757274, rs2383206 and rs1333049, were strongly associated with early-onset CHD (p = 2.7 x 10(-6), 2.7 x 10(-6), 3.8 x 10(-7), respectively). Analysis of haplotypes by the TRANSMIT program also showed that the GGC haplotype was associated with early-onset CHD (p=7.9 x 10(-7)). In conclusion, using a family-based approach in the Irish population, we have confirmed previous reports of association between a region on chromosome 9p21.3 and early-onset CHD. | 18,957,718 |
Ergonomics for children: an educational program for elementary school. | Studies indicate that musculoskeletal discomfort and back pain problems are evident not only in adults, but also in children [11,13]. We believe that educating towards a balanced-posture, body-function and movement patterns, as well as their ergonomic implications, can minimize and even prevent these problems. Such an ergonomics awareness educational program has to start at childhood and should be an integral part of the curriculum in the schools. This article presents the educational program "Ergonomics, Movement and Posture" (EMP), which is taught in elementary schools by Physical Education (PE) students of the Kibbutzim College of Education in Israel, as part of their practicum. Although there has been no formal evaluation of the effectiveness of the program, so far, participating children, their parents, the teachers and the principles have offered positive feedback. | 18,957,743 |
Behaviors of physiologically active bacteria in water environment and chlorine disinfection. | Direct microscopic methods using several fluorescent staining were applied to estimate the proportion of physiologically active bacteria in the water environment and evaluate the efficacy of disinfection with chlorine. 4',6-diamidino-2-phenylindole (DAPI) was used to determine total bacterial numbers, and 5-cyano-2,3-ditolyl tetrazolium chloride (CTC) was chosen for direct detection of respiring bacteria. BacLight kit was used to assess bacterial membrane integrity. Bacteria with growth potential were enumerated using the DVC method and microcolony technique. The total bacterial number in river was 8 x 10(6)-3 x 10(10) cells/mL, and colony forming units on R2A medium were 1 x 10(4)-4 x 10(5) cfu/mL. In the case of wastewater treatment plant, 1-10% of total bacterial cells could form colonies. Physiologically active bacteria in river and wastewater treatment plant determined by fluorescent staining were much higher than those obtained by plate counting. The effect of chlorine on the physiological viability of Escherichia coli was also investigated. Microscopic viable bacteria were even more chlorine resistant than culturable bacteria. The inactivation rate coefficients of direct viable bacteria were one-second to third those of culturable bacteria. | 18,957,745 |
Codigestion of manure and industrial organic waste at centralized biogas plants: process imbalances and limitations. | The present study focuses on process imbalances in Danish centralized biogas plants treating manure in combination with industrial waste. Collection of process data from various full-scale plants along with a number of interviews showed that imbalances occur frequently. High concentrations of ammonia or long chain fatty acids is in most cases expected to be the cause of microbial inhibitions/imbalances while foaming in the prestorage tanks and digesters is the most important practical process problem at the plants. A correlation between increased residual biogas production (suboptimal process conditions) and high fractions of industrial waste in the feedstock was also observed. The process imbalances and suboptimal conditions are mainly allowed to occur due to 1) inadequate knowledge about the waste composition, 2) inadequate knowledge about the waste degradation characteristics, 3) inadequate process surveillance, especially with regard to volatile fatty acids, and 4) insufficient pre-storage capacity causing inexpedient mixing and hindering exact dosing of the different waste products. | 18,957,768 |
Measuring the effectiveness of performance-based training. | This article describes a statistical analysis of small water systems' turbidity data within the framework of a logic model for the USEPA's Performance-Based Training (PBT) program. The logic model shows the theoretical linkages between optimization training for small system operators; operator application of optimization techniques; improvements in plant filtration performance; and public health protection. The analysis comprised two phases. For the first phase, the authors used Bayesian analysis of turbidity data to test the statistical significance of changes in finished water quality resulting from training for small water system operators. For the second phase, the authors estimated the potential health benefits resulting from measured improvements in filtration performance. Considering only the improved removal of the pathogen Cryptosporidium, the expected annual health benefit of PBT is about ten fewer cases of infection per thousand persons served (within a 95% credible interval 0 to 18 fewer infections), though there may be benefits associated with the removal of other pathogens. The article also describes factors contributing to uncertainty in the estimated potential health benefits. The proposed two-phase approach supports the USEPA's development of drinking water program indicators which are meaningful, measurable, broadly applicable and change-sensitive. | 18,957,784 |
Mechanical strain increases expression of type XII collagen in murine osteoblastic MC3T3-E1 cells. | In adult mouse, the mRNA corresponding to the alpha1 chain of type XII collagen (alpha 1(XII)) is predominantly detected in the bone. Additionally, murine osteoblastic cells, MC3T3-E1, increased the mRNA level of alpha 1(XII) response to the mechanical strain in the stretch culture system. Cyclic stretch stress resulted in a threefold increase in mRNA level of alpha 1(XII) as compared to the control experiment in MC3T3-E1. Transient transfection assays employing a reporter construct, together with site-directed mutagenesis studies, suggested that the AP-1 binding site in the first exon of mouse alpha 1(XII) gene is important for stretch stress-mediated upregulation of alpha 1(XII) expression. Electrophoretic mobility shift assay and associated antibody supershift experiments showed that stretch stress promotes the binding of c-Jun and JunD. Further chromatin immunoprecipitation experiments confirmed the participation of these transcription factors in the region. Also, the exogenous induction of the dominant negative form of c-Jun canceled the effect of stretch stress on the stimulation of the alpha 1(XII) gene. Here, we reported a potential responsive element to the stretch stress in mouse alpha 1(XII) gene. These data will provide new information on the mechanical strain-mediated transcriptional control of alpha 1(XII)-mediated fibrillogenesis in the bone. | 18,957,791 |
The metabolic syndrome as a concept of adipose tissue disease. | The metabolic syndrome is a constellation of interrelated metabolic risk factors that appear to directly promote the development of diabetes and cardiovascular disease. However, in 2005, the American Diabetes Association and the European Association for the Study of Diabetes jointly stated that no existing definition of the metabolic syndrome meets the criteria of a syndrome, and there have been endless debates on the pros and cons of using the concept of this syndrome. The controversy may stem from confusion between the syndrome and obesity. Obesity is an epidemic, essentially contagious disease caused by an environment of excess nutritional energy and reinforced by deeply rooted social norms. The epidemic of obesity should be prevented or controlled by social and political means, similar to the approaches now being taken to combat global warming. The diagnosis of metabolic syndrome is useless for this public purpose. The purpose of establishing criteria for diagnosing metabolic syndrome is to find individuals who are at increased risk of diabetes and cardiovascular disease and who require specific therapy including diet and exercise. The syndrome may be an adipose tissue disease different from obesity; in that case, it would be characterized by inflammation clinically detected through systemic inflammatory markers such as high-sensitivity C-reactive protein and insulin resistance reflecting histological changes in adipose tissue. However, many problems in defining the optimal diagnostic criteria remain unresolved. | 18,957,797 |
Monosynaptic excitatory connection from the rostral ventrolateral medulla to sympathetic preganglionic neurons revealed by simultaneous recordings. | To directly investigate whether a monosynaptic connection exists between neurons in the rostral ventrolateral medulla (RVLM) and sympathetic preganglionic neurons (SPNs), we used simultaneous extracellular recordings of RVLM neurons and whole-cell patch-clamp recordings of SPNs at the Th2 level and analyzed them by spike-triggered averaging. We averaged 200 sweeps of membrane potentials in SPN triggered by the spikes in the RVLM neuron. No clear postsynaptic potentials were detected in the averaged wave of SPNs before angiotensin II (Ang II) superfusion, whereas during superfusion with Ang II (6 micromol/L) on the medulla oblongata side alone excitatory postsynaptic potentials (EPSPs) were clearly found in the SPN of 3 out of 10 pairs at 40 +/- 1 ms after the averaged triggering spike in the RVLM neuron. We consider them to be monosynaptic EPSPs, because 1) the averaged EPSPs exhibited a sharp rise time, 2) the onset latency of the averaged EPSPs in the SPNs after the trigger spike in the RVLM was the same as the latency of the antidromic action potentials in the RVLM neurons in response to electrical stimulation of the SPNs, and 3) the amplitude of the averaged EPSPs was over 2 mV. In summary, combining simultaneous recording and spike-triggered averaging allowed us to demonstrate a monosynaptic excitatory connection between a single RVLM neuron and a single SPN in the thoracic spinal cord. Such connections provide the basis for the maintenance of sympathetic tone and the integrative reflex that relays through the RVLM. The results explain the mechanism by which Ang II in the RVLM area increases peripheral sympathetic activity and blood pressure. | 18,957,816 |
Dose-response relationship for induction of ovarian tumors in mice irradiated during prenatal, early postnatal and elder periods. | Female B6C3F1 mice were irradiated at day 17 prenatal period, day 0, 7, 35, 105, 240, 365 and 550 postnatal period with doses of 0.10 to 5.70 Gy gamma rays from (137)Cs. All mice were allowed to live through their entire life spans under a specific-pathogen free condition. The excess relative risk for prevalence at the time of death of ovarian tumors was used as a comprehensive measure of radiation effect. The excess relative risks at 1 Gy were estimated for all irradiated groups based on the dose-response relationships and compared to each other. A marked increase in susceptibility was found during the age between day 17 prenatal and day 0 postnatal period. A drastic decrease in susceptibility was observed during the period between day 105 and day 240. The shape of the dose-response curve was downward concave in mice irradiated at day 0, 7, 35 or 105 postnatal period, whereas, the downward curvature of dose-response was not observed in mice irradiated at day 17 prenatal period, day 240, 365 or 550 postnatal period. It has become obvious that mice of the early postnatal, pre-puberty and young adult periods are highly susceptible to induction of ovarian tumors by gamma rays. | 18,957,829 |
[Relationships of positive and negative affectivity to sleep quality in Japanese civil servants: 3-year follow-up study]. | We conducted this longitudinal study to evaluate the relationships of positive and negative affectivity (Affect Balance Scale) to sleep quality among civil servants. For this study we evaluated 827 civil servants of T city in Toyama prefecture in the springs of 2001 (Baseline) and 2004 with complete information in both phases of the study. Based on the median score at each phase, we divided Affect Balance Scale (ABS) scores into high and low groups. We conducted logistic regression analysis to determine the odds ratios (OR) of 3-yr follow-up sleep quality by baseline and follow-up ABS scores. After adjusting for baseline sleep quality scores, age, sex, employment, job strain, and exercise habits, participants who had high ABS scores were more likely (OR: 3.13, 95% confidence interval (CI): 1.78-5.53) to have better sleep quality than those with low ABS scores at both phases. In addition, participants with low ABS scores at baseline and high ABS scores 3 yr later had better sleep quality (OR: 1.81, 95%CI: 1.02-3.20) than those with low ABS scores at both phases. These findings substantiate the relationships of positive and negative affectivity to sleep quality. Improving the affect balance condition as well as maintaining good affect balance condition may be important determinants of sleep quality in civil servants. | 18,957,834 |
Effect of insulin-like growth factor-I gene therapy on the somatotropic axis in experimental prolactinomas. | Insulin-like growth factor-I (IGF-I) provides a physiologic feedback effect within the somatotropic axis. Gene therapy was implemented in young female Sprague-Dawley rats which received 2 pituitary stereotaxic injections of a control recombinant adenoviral vector expressing green fluorescent protein (RAd-GFP) or IGF-I (RAd-IGF-I). The animals were sacrificed 7 days after injection. Previously, on day -23, the experimental groups received subcutaneous implants of 17-beta estradiol. Morphometric analysis revealed that the somatotrope cells in estrogen-treated rats without stereotaxic injections showed a significant (p < 0.01) increase in the cell size compared with intact controls (59.9 +/- 1.1 vs. 42.9 +/- 1.2 microm(2)) and had a significant (p < 0.05) decrease in cell density with respect to intact animals (10.5 +/- 0.1 vs. 19.7 +/- 1.7). The treatment of pituitary adenomas with RAd-IGF-I induced a significant (p < 0.05) decrease in cell size with respect to E(2) + RAd-GFP (51.3 +/- 0.3 vs. 58.9 +/- 0.3 microm(2)) and no changes in cell density compared with RAd-GFP-injected animals (12.8 +/- 1.7 vs. 10.5 +/- 0.1). Serum growth hormone was higher (p < 0.01) in estrogen-treated animals versus controls (146.7 +/- 6 vs. 73.9 +/- 9 ng/ml). In rats carrying estrogen-induced adenomas, RAd-IGF-I injection induced a significant (p < 0.05) decrease in serum growth hormone compared to RAd-GFP-injected animals (107.5 +/- 7 vs. 142.4 +/- 9 ng/ml). IGF-I gene therapy appears to be an effective approach for the treatment of experimental somatomammotropic pituitary tumors and could be potentially useful as an adjuvant of conventional therapies. | 18,957,836 |
Time delay between onset of symptoms and diagnosis in pulmonary thromboembolism. | Although pulmonary thromboembolism is usually considered as an acute illness, delayed presentations are fairly common. The purpose of this study was to investigate delays to presentation/diagnosis and their likely correlation with patients' clinical and radiographic findings in pulmonary thromboembolism. All cases of pulmonary embolism diagnosed in our hospital between March 2002 and May 2006 were reviewed for the date of symptom onset, the dates of presentation and diagnosis, clinical findings, localization of embolism in pulmonary vascular tree and pleuropulmonary changes arising secondary to thrombotic occlusion. The parameters related to presentation delays were analyzed using a Mann-Whitney U test and logistic regression analysis. Of the 178 patients enrolled, 30.4% presented to hospital 1 week after the start of their symptoms and there was an average of 8.4 +/- 11.4 days' (median 4 days, range 0-75) delay to presentation. The delay from presentation to diagnosis was 0.9 +/- 1.9 days (median 0, range 0-16). Patients with hypotension, respiratory rate >20 and atelectasis in spiral CT presented earlier. However, no correlation was found between delays and the level of thromboembolic occlusion in pulmonary artery. Pulmonary thromboembolism should be considered not only in an acute setting, but also in patients with prolonged respiratory symptoms, since there was a significant delay to presentation amongst our patients. The presence of hypotension and a high respiratory frequency was clearly associated with early presentation. | 18,957,839 |
Protein restriction during pregnancy induces hypertension and impairs endothelium-dependent vascular function in adult female offspring. | Intrauterine undernutrition plays a role in the development of adult hypertension. Most studies are done in male offspring to delineate the mechanisms whereby blood pressure may be raised; however, the vascular mechanisms involved in female offspring are unclear. Female offspring of pregnant Sprague-Dawley rats fed either a control (C; 18%) or a low-protein (LP; 6%) diet during pregnancy were used. Birth weight and later growth were markedly lower in LP than in C offspring. LP offspring exhibited impaired estrous cyclicity with increased mean arterial pressure. Hypotensive response to acetylcholine (ACh) and the hypertensive response to phenylephrine (PE) were greater in LP than in C rats. N-nitro-L-arginine methyl ester (L-NAME) induced greater hypertensive responses in C than in LP rats. Endothelium-intact mesenteric arteries from LP offspring exhibited increased contractile responses to PE and reduced vasodilation in response to ACh. In endothelium-denuded arteries, relaxation responses to sodium nitroprusside were similar in both groups. Basal and ACh-induced increase in vascular nitrite/nitrate production was lower in LP than in C offspring. L-NAME or 1H-1,2,4-oxadiazolo-4,3-quinoxalin-1-one inhibited ACh relaxations and enhanced PE contractions in C offspring, but had minimal effect in LP rats. The decreased NO-mediated vascular response might explain the increased vascular contraction and arterial pressure in female offspring with low birth weight. | 18,957,856 |
Metagenomics for mining new genetic resources of microbial communities. | Recent progress has revealed that the capture of genetic resources of complex microbial communities in metagenome libraries allows the discovery of a richness of new enzymatic diversity that had not previously been imagined. Activity-based screening of such libraries has demonstrated that this new diversity is not simply variations on known sequence themes, but rather the existence of entirely new sequence classes and novel functionalities. This new diversity, the surface of which has thus far only been scratched, constitutes potential for a wealth of new and improved applications in industry, medicine, agriculture, etc., and promises to facilitate in a significant manner our transition to a sustainable society, by contributing to the transition to renewable sources of energy, chemicals and materials, the lowering of pollutant burdens, lower processes energies, etc. Current bottlenecks in metagenomics include insufficient functional characterization and amplifying non-validated annotations of proteins in databases. | 18,957,866 |
Implantation of dedifferentiated fat cells ameliorates habu snake venom-induced chronic renal dysfunction in tenascin-C-deficient mice. | We established dedifferentiated fat (DFAT) cells from mature adipocytes that differentiate to multiple lineages and have characteristics similar to those of mesenchymal stem cells. In this study, we evaluated the effect of implantation of DFAT cells on habu snake venom (HSV)-induced renal dysfunction in tenascin-C knockout (TC-KO) mice. Cultured DFAT cells were incubated with PDGF-BB and immunostained with anti-desmin antibody to determine mesenchymal differentiation. HSV was injected, and DFAT cells from GFP mice were implanted in TC-KO mice via the tail vein. Expression of tenascin-C, transforming growth factor-beta(1) (TGF-beta1), and fibronectin mRNAs in the renal cortex were evaluated by RT-PCR analysis. Cultured DFAT cells showed desmin immunostaining in response to PDGF-BB.HSV injection induced glomerulosclerosis, which was significantly improved by implantation of DFAT cells. Serum BUN increased after HSV injection and was significantly decreased by implantation of DFAT cells. Tenascin-C mRNA was detected in the renal cortex in implanted mice. Expression of TGF-beta1 and fibronectin mRNAs increased in the renal cortex after HSV injection, and was significantly decreased by implantation of DFAT cells. DFAT cells may provide a source for cell therapy for severe progressive renal disease. | 18,957,871 |
New approaches to target microsomal triglyceride transfer protein. | Microsomal triglyceride transfer protein (MTP), a chaperone for the biosynthesis of apolipoprotein B lipoproteins and CD1d, is a therapeutic candidate to decrease plasma lipids and to diminish inflammation. MTP inhibition increases plasma transaminases and tissue lipids, and therefore new approaches are needed to avoid them. Inositol requiring enzyme1beta has been identified as a novel intestine-specific regulator of MTP. A new function of MTP in cholesterol ester biosynthesis has been reported. The importance of the phospholipid transfer activity of MTP in the lipidation of apolipoprotein B and CD1d has been indicated. Diurnal variations in MTP expression and its induction by food availability have been observed. On the basis of these and other findings, we propose that upregulation of inositol requiring enzyme 1beta, a combined reduction of cellular free cholesterol or triglyceride or both and MTP activity, specific inhibition of phospholipid or triglyceride transfer activities, and targeting of apolipoprotein B-MTP protein-protein interactions might be pursued to avoid some of the side effects associated with the inhibition of triglyceride transfer activity of MTP. We further speculate that short-lived MTP antagonists may be useful in controlling plasma and tissue lipids and in avoiding steatosis. We have highlighted the importance of addressing the causal relationship between MTP inhibition and aberrant elevations in plasma liver enzymes. The proposed approaches may show that MTP targeting is a viable approach to lower plasma lipids. | 18,957,879 |
The trials and tribulations of the treatment of nonalcoholic fatty-liver disease. | To review published clinical trials, with a focus on those of randomized design, of the management of nonalcoholic fatty-liver disease (NAFLD), an increasing complication of the obesity epidemic. There is increasing recognition that cardiovascular risk issues are associated with NAFLD. Clinical trials of management of NAFLD have focused mainly on hepatic complications. The weight of data point to greatest biochemical and histological benefit with weight-loss measures and thiazolidinediones, but further trials are needed to characterize the benefits and risks of the latter agents. There is currently insufficient trial data to recommend other strategies for treating NAFLD. There is an emerging need for early multiple factor risk intervention, emphasizing cardiometabolic risk and weight management, in addition to minimizing risk of hepatic complications. Given the strong association of NAFLD with the metabolic syndrome, early recognition, assessment and management of NAFLD is essential. The management emphasizes weight reduction and attention to cardiometabolic risk factors, similar to recommendations for management of the metabolic syndrome. Future research, guided by increasing knowledge of the pathogenetic factors driving the condition, should clarify the role of other therapies for reducing hepatic and cardiovascular morbidity associated with NAFLD. | 18,957,882 |
Role of glial cells in the functional expression of LL-37/rat cathelin-related antimicrobial peptide in meningitis. | Antimicrobial peptides are intrinsic to the innate immune system in many organ systems, but little is known about their expression in the central nervous system. We examined cerebrospinal fluid (CSF) and serum from patients with active bacterial meningitis to assess antimicrobial peptides and possible bactericidal properties of the CSF. We found antimicrobial peptides (human cathelicidin LL-37) in the CSF of patients with bacterial meningitis but not in control CSF. We next characterized the expression, secretion, and bactericidal properties of rat cathelin-related antimicrobial peptide, the homologue of the human LL-37, in rat astrocytes and microglia after incubation with different bacterial components. Using real-time polymerase chain reaction and Western blotting, we determined that supernatants from both astrocytes and microglia incubated with bacterial component supernatants had antimicrobial activity. The expression of rat cathelin-related antimicrobial peptide in rat glial cells involved different signal transduction pathways and was induced by the inflammatory cytokines interleukin 1beta and tumor necrosis factor. In an experimental model of meningitis, infant rats were intracisternally infected with Streptococcus pneumoniae, and rat cathelin-related antimicrobial peptide was localized in glia, choroid plexus, and ependymal cells by immunohistochemistry. Together, these results suggest that cathelicidins produced by glia and other cells play an important part in the innate immune response against pathogens in central nervous system bacterial infections. | 18,957,897 |
[The physician-patient relationship in chronic disease management]. | The relationship between patients and clinicians is a key element in the management of chronic diseases. With the objective of a more efficient communication, the clinician should know his own personality but also the patient personality. The organisation of the consultation, of the waiting room and of the secretary has to facilitate this relationship. The amelioration of this relationship is usefulness only for the clinician in particularly complicated cases but also for the patients suffering from chronic diseases. | 18,957,911 |
[News in trabeculoplasty]. | The main objection to argon laser trabeculoplasty is collateral tissular injury, requiring hazardous repeated sessions if tonometric efficacy decreases. Selective trabeculoplasty could allow reliably effective iterative sessions because it is relatively harmless to tissues. Two other physical methods are on the market, although they are still being investigated, which also allow repeated treatments with minimal trabecular impairment. Titanium:sapphire laser trabeculoplasty consists of a very short pulse duration, with a wavelength penetrating deeply into the trabecula meshwork; the first results indicate similar intraocular pressure reduction as that obtained with argon trabeculoplasty and selective trabeculoplasty, but point out a possible risk of a paradoxical pressure rise during the days following the procedure. Pneumotrabeculoplasty is a procedure that uses ocular stretching by suction, which could finally provide a long-lasting decrease in intraocular pressure, less than that obtained with lasers, but its harmlessness is proved and its cost much lower. | 18,957,920 |
[Tolerance to fixed combinations]. | Four classes of drugs are mainly used for glaucoma medical therapy: beta-blockers, prostaglandin analogs, alpha-2 agonists, and carbonic anhydrase inhibitors. Clinicians can prescribe fixed combinations that associate two drugs from two different classes that have been available for a long time. Tolerance of fixed combinations seems to be better than the separate instillation of drugs, but it is interesting to review the adverse events and the contraindications of these drugs. | 18,957,921 |
SNP analyses of postprandial responses in (an)orexigenic hormones and feelings of hunger reveal long-term physiological adaptations to facilitate homeostasis. | The postprandial responses in (an)orexigenic hormones and feelings of hunger are characterized by large inter-individual differences. Food intake regulation was shown earlier to be partly under genetic control. This study aimed to determine whether the postprandial responses in (an)orexigenic hormones and parameters of food intake regulation are associated with single nucleotide polymorphisms (SNPs) in genes encoding for satiety hormones and their receptors. Peptide YY (PYY), glucagon-like peptide 1 and ghrelin levels, as well as feelings of hunger and satiety, were determined pre- and postprandially in 62 women and 41 men (age 31+/-14 years; body mass index 25.0+/-3.1 kg/m(2)). Dietary restraint, disinhibition and perceived hunger were determined using the three-factor eating questionnaire. SNPs were determined in the GHRL, GHSR, LEP, LEPR, PYY, NPY, NPY2R and CART genes. The postprandial response in plasma ghrelin levels was associated with SNPs in PYY (215G>C, P<0.01) and LEPR (326A>G and 688A>G, P<0.01), and in plasma PYY levels with SNPs in GHRL (-501A>C, P<0.05) and GHSR (477G>A, P<0.05). The postprandial response in feelings of hunger was characterized by an SNP-SNP interaction involving SNPs in LEPR and NPY2R (668A>G and 585T>C, P<0.05). Dietary restraint and disinhibition were associated with an SNP in GHSR (477G>A, P<0.05), and perceived hunger with SNPs in GHSR and NPY (477G>A and 204T>C, P<0.05). Part of the inter-individual variability in postprandial responses in (an)orexigenic hormones can be explained by genetic variation. These postprandial responses represent either long-term physiological adaptations to facilitate homeostasis or reinforce direct genetic effects. | 18,957,934 |
A large-scale functional approach to uncover human genes and pathways in Drosophila. | We demonstrate the feasibility of performing a systematic screen for human gene functions in Drosophila by assaying for their ability to induce overexpression phenotypes. Over 1 500 transgenic fly lines corresponding to 236 human genes have been established. In all, 51 lines are capable of eliciting a phenotype suggesting that the human genes are functional. These heterologous genes are functionally relevant as we have found a similar mutant phenotype caused either by a dominant negative mutant form of the human ribosomal protein L8 gene or by RNAi downregulation of the Drosophila RPL8. Significantly, the Drosophila RPL8 mutant can be rescued by wild-type human RPL8. We also provide genetic evidence that Drosophila RPL8 is a new member of the insulin signaling pathway. In summary, the functions of many human genes appear to be highly conserved, and the ability to identify them in Drosophila represents a powerful genetic tool for large-scale analysis of human transcripts in vivo. | 18,957,936 |
Genome-wide association scan for five major dimensions of personality. | Personality traits are summarized by five broad dimensions with pervasive influences on major life outcomes, strong links to psychiatric disorders and clear heritable components. To identify genetic variants associated with each of the five dimensions of personality we performed a genome-wide association (GWA) scan of 3972 individuals from a genetically isolated population within Sardinia, Italy. On the basis of the analyses of 362 129 single-nucleotide polymorphisms we found several strong signals within or near genes previously implicated in psychiatric disorders. They include the association of neuroticism with SNAP25 (rs362584, P=5 x 10(-5)), extraversion with BDNF and two cadherin genes (CDH13 and CDH23; Ps<5 x 10(-5)), openness with CNTNAP2 (rs10251794, P=3 x 10(-5)), agreeableness with CLOCK (rs6832769, P=9 x 10(-6)) and conscientiousness with DYRK1A (rs2835731, P=3 x 10(-5)). Effect sizes were small (less than 1% of variance), and most failed to replicate in the follow-up independent samples (N up to 3903), though the association between agreeableness and CLOCK was supported in two of three replication samples (overall P=2 x 10(-5)). We infer that a large number of loci may influence personality traits and disorders, requiring larger sample sizes for the GWA approach to confidently identify associated genetic variants. | 18,957,941 |
The brain expression of genes involved in inflammatory response, the ribosome, and learning and memory is altered by centrally injected lipopolysaccharide in mice. | Neuroinflammation plays a role in the progression of several neurodegenerative disorders. We used a lipopolysaccharide (LPS) model of neuroinflammation to characterize the gene expression changes underlying the inflammatory and behavioral effects of neuroinflammation. A single intracerebroventricular injection of LPS (5 microg) was administered into the lateral ventricle of mice and, 24 h later, we examined gene expression in the cerebral cortex and hippocampus using microarray technology. Gene Ontology (GO) terms for inflammation and the ribosome were significantly enriched by LPS, whereas GO terms associated with learning and memory had decreased expression. We detected 224 changed transcripts in the cerebral cortex and 170 in the hippocampus. Expression of Egr1 (also known as Zif268) and Arc, two genes associated with learning and memory, was significantly lower in the cortex, but not in the hippocampus, of LPS-treated animals. Overall, altered expression of these genes may underlie some of the inflammatory and behavioral effects of neuroinflammation. | 18,957,951 |
International standards to document remaining autonomic function after spinal cord injury. | Experts opinions consensus. To develop a common strategy to document remaining autonomic neurologic function following spinal cord injury (SCI). The impact of a specific SCI on a person's neurologic function is generally described through use of the International Standards for the Neurological Classification of SCI. These standards document the remaining motor and sensory function that a person may have; however, they do not provide information about the status of a person's autonomic function. Based on this deficiency, the American Spinal Injury Association (ASIA) and the International Spinal Cord Society (ISCoS) commissioned a group of international experts to develop a common strategy to document the remaining autonomic neurologic function. Four subgroups were commissioned: bladder, bowel, sexual function and general autonomic function. On-line communication was followed by numerous face to face meetings. The information was then presented in a summary format at a course on Measurement in Spinal Cord Injury, held on June 24, 2006. Subsequent to this it was revised online by the committee members, posted on the websites of both ASIA and ISCoS for comment and re-revised through webcasts. Topics include an overview of autonomic anatomy, classification of cardiovascular, respiratory, sudomotor and thermoregulatory function, bladder, bowel and sexual function. This document describes a new system to document the impact of SCI on autonomic function. Based upon current knowledge of the neuroanatomy of autonomic function this paper provides a framework with which to communicate the effects of specific spinal cord injuries on cardiovascular, broncho-pulmonary, sudomotor, bladder, bowel and sexual function. | 18,957,962 |
Phase Ib trial of mutant herpes simplex virus G207 inoculated pre-and post-tumor resection for recurrent GBM. | We have previously demonstrated safety of G207, a doubly mutated (deletion of both gamma(1)34.5 loci, insertional inactivation of U(L)39) herpes simplex virus (HSV) for patients stereotactically inoculated in enhancing portions of recurrent malignant gliomas. We have now determined safety of two inoculations of G207, before and after tumor resection. Inclusion criteria were histologically proven recurrent malignant glioma, Karnofsky score >or=70, and ability to resect the tumor without ventricular system breach. Patients received two doses of G207 totaling 1.15 x 10(9) plaque-forming units with 13% of this total injected via a catheter placed stereotactically in the tumor. Two or five days later, tumor was resected en bloc with catheter in place. The balance of G207 dose was injected into brain surrounding the resection cavity. Six patients with recurrent glioblastoma multiforme were enrolled. Two days after the second G207 inoculation, one patient experienced transient fever, delirium, and hemiparesis, which entirely resolved on high-dose dexamethasone. No patient developed HSV encephalitis or required treatment with acyclovir. Radiographic and neuropathologic evidence suggestive of antitumor activity is reported. Evidence of viral replication was demonstrated. G207 appears safe for multiple dose delivery, including direct inoculation into the brain surrounding tumor resection cavity. | 18,957,964 |
A new potent secondary amphipathic cell-penetrating peptide for siRNA delivery into mammalian cells. | RNA interference constitutes a powerful tool for biological studies, but has also become one of the most challenging therapeutic strategies. However, small interfering RNA (siRNA)-based strategies suffer from their poor delivery and biodistribution. Cell-penetrating peptides (CPPs) have been shown to improve the intracellular delivery of various biologically active molecules into living cells and have more recently been applied to siRNA delivery. To improve cellular uptake of siRNA into challenging cell lines, we have designed a secondary amphipathic peptide (CADY) of 20 residues combining aromatic tryptophan and cationic arginine residues. CADY adopts a helical conformation within cell membranes, thereby exposing charged residues on one side, and Trp groups that favor cellular uptake on the other. We show that CADY forms stable complexes with siRNA, thereby increasing their stability and improving their delivery into a wide variety of cell lines, including suspension and primary cell lines. CADY-mediated delivery of subnanomolar concentrations of siRNA leads to significant knockdown of the target gene at both the mRNA and protein levels. Moreover, we demonstrate that CADY is not toxic and enters cells through a mechanism which is independent of the major endosomal pathway. Given its biological properties, we propose that CADY-based technology will have a significant effect on the development of fundamental and therapeutic siRNA-based applications. | 18,957,965 |
Consumption of 'extra' foods by Australian adults: types, quantities and contribution to energy and nutrient intakes. | To identify the types and quantities of 'extra' foods, or energy-dense, nutrient-poor foods, consumed by Australian adults, and assess their contribution to total energy and nutrient intakes. We used 24-h recall data from 10 851 adults, aged 19 years and over, who participated in the nationally representative 1995 National Nutrition Survey. 'Extra' foods were defined using principles outlined in the Australian Guide to Healthy Eating and by applying cut points for maximum amounts of fat and sugar within each food category. 'Extra' foods contributed to 36% of daily energy intake with the highest contributors being fried potatoes (2.8%), margarine (2.6%), cakes and muffins (2.5%), beer (2.4%), sugar-sweetened soft drinks (2.4%), and meat pies (2.2%). Both age and sex were important determinants of 'extra' foods intake; younger adults were more likely to consume sugar-sweetened soft drinks, fried potatoes, meat pies and savoury pastries, pizza, crisps, lollies and chocolate; whereas older adults were more likely to consume sweet and savoury biscuits, cakes and muffins, margarine and butter. In all age groups, 'extra' foods contributed more to energy intake for men than women. Overall, 'extra' foods contributed 16% protein, 41% total fat, 41% saturated fat, 47% sugar and approximately 20% of selected micronutrients to the diet. 'Extra' foods contribute excessively to the energy, fat and sugar intakes of Australian adults, while providing relatively few micronutrients. This is of concern for the increasing risk of overweight and chronic disease and poor micronutrient status. | 18,957,970 |
Effect of the glycemic index of carbohydrates on day-long (10 h) profiles of plasma glucose, insulin, cholecystokinin and ghrelin. | Low glycemic index (GI) carbohydrates have been linked to increased satiety. The drive to eat may be mediated by postprandial changes in glucose, insulin and gut peptides. To investigate the effect of a low and a high GI diet on day-long (10 h) blood concentrations of glucose, insulin, cholecystokinin (CCK) and ghrelin (GHR). Subjects (n=12) consumed a high and a low GI diet in a randomized, crossover design, consisting of four meals that were matched for macronutrients and fibre, and differed only in carbohydrate quality (GI). Blood was sampled every 30-60 min and assayed for glucose, insulin, CCK and GHR. The high GI diet resulted in significantly higher glucose and insulin mean incremental areas under the curve (IAUC, P=0.027 and P=0.001 respectively). CCK concentration was 59% higher during the first 7 h of the low GI diet (394+/-95 pmol/l min) vs the high GI diet (163+/-38 pmol/l min, P=0.046), but there was no difference over 10 h (P=0.224). GHR concentration was inversely correlated with insulin concentration (Pearson correlation -0.48, P=0.007), but did not differ significantly between the low and high GI diets. Mixed meals of lower GI are associated with lower day-long concentrations of glucose and insulin, and higher CCK after breakfast, morning tea and lunch. This metabolic profile could mediate differences in satiety and hunger seen in some, but not all, studies. | 18,957,972 |
Transient widespread blood-brain barrier alterations after cerebral photothrombosis as revealed by gadofluorine M-enhanced magnetic resonance imaging. | Magnetic resonance imaging (MRI) is a powerful tool to assess brain lesions, but currently available contrast agents are limited in the assessment of cellular and functional alterations. By use of the novel MRI contrast agent gadofluorine M (Gf) we report on imaging of transient and widespread changes of blood-brain barrier (BBB) properties as a consequence of focal photothrombotic brain lesions in rats. After i.v. application, Gf led to bright contrast in the lesions, but also the entire ipsilateral cortex on T1-weighted MRI. In contrast, enhancement after application of gadolinium diethylenetriamine-pentaacetic acid (Gd-DTPA), a common clinical indicator of BBB leakage was restricted to the lesions. Remote Gf enhancement was restricted in time to the first 24 h after photothrombosis and corresponded to a transient breakdown of the BBB as revealed by extravasation of the dye Evans blue. In conclusion, our study shows that Gf can visualize subtle disturbances of the BBB in three dimensions not detectable by Gd-DTPA. Upon entry into the central nervous system Gf most likely is locally trapped by interactions with extracellular matrix proteins. The unique properties of Gf hold promise as a more sensitive contrast agent for monitoring BBB disturbances in neurologic disorders, which appear more widespread than anticipated previously. | 18,957,988 |
GABA synapses mediate neuroprotection after ischemic and epsilonPKC preconditioning in rat hippocampal slice cultures. | Delayed neuroprotection against ischemic challenges is conferred by both ischemic preconditioning (IPC) and preconditioning by activation of the epsilon-isoform of protein kinase C (epsilonPKC-PC). In vivo, ischemic preconditioning enhances GABA release and ameliorates glutamate release during lethal cerebral ischemia. We tested the hypothesis that IPC and epsilonPKC-PC confer neuroprotection by GABA synapses in rat organotypic hippocampal slices. Ischemic preconditioning or epsilonPKC-PC was induced with 15 mins oxygen-glucose deprivation (OGD) or psiepsilonRACK, a selective epsilonPKC activator; and test ischemia consisted of 40 mins OGD. At the time of peak neuroprotection (48 h after preconditioning), we recorded GABA(A) receptor-mediated miniature postsynaptic currents (GABA mPSCs) in vulnerable CA1 pyramidal neurons using whole-cell voltage clamp techniques. The frequency and amplitude of GABA mPSCs significantly increased 48 h after IPC. In contrast, epsilonPKC-PC enhanced only the amplitude of GABA mPSCs with no effect on frequency. We next asked if neuroprotection depended on these changes in GABA synapses. Weak antagonism of the GABA(A) receptor with bicuculline (100 nmol/L) decreased the amplitude of GABA mPSCs by 20.9+/-6.1%. When applied during test ischemia, 100 nmol/L bicuculline abolished neuroprotection conferred by either IPC or epsilonPKC-PC. We conclude that neuroprotection conferred by preconditioning depends on functional modifications of GABA synapses. | 18,957,990 |
Children's inhalation exposure to methamidophos from sprayed potato fields in Washington State: exploring the use of probabilistic modeling of meteorological data in exposure assessment. | We examined the significance of meteorology and postspray volatilization of methamidophos (an organophosphorus insecticide) in assessing potential inhalation risk to children in an agricultural community. We combined fluxes from sources and dispersion modeling with a range of possible local meteorology to create output to study the variability in potential community exposure as a result of changing temperature, wind speeds and wind directions. This work is based on an aerial spray drift study where air sampling measurements of methamidophos were made before, during and after a spray event were used to examine acute inhalation risk for children living in an Eastern Washington State community in close proximity (between 15 and 200 m) to sprayed potato fields. We compared the measured average air concentrations of methamidophos in the community to a "no observed adverse effect level" for subchronic inhalation to characterize acute and subchronic inhalation risks. The baseline estimates of inhalation exposure were below Environment Protection Agency's (EPA) level of concern based on a target margin of exposure of 300. As meteorological conditions during and after spraying influence the amount of material moving into areas where children reside we used historical meteorological data to drive model simulations that predicted likely air residue concentrations under different wind and temperature conditions. We also added variability to the decay constant and initial emission fluxes to create a 2-D simulation of estimated air concentrations in the community near the fields. This work provides a methodological framework for the assessment of air concentrations of pesticides from agricultural sprays in the absence of extended measurements, although including variability from meteorological conditions. The deterministic as well as the probabilistic risk analyses in this study indicated that postspray volatilization in the specific spray situation analyzed (methamidophos applied on potato fields in Eastern Washington) did not pose acute or subchronic risks as defined by the EPA. However, this study did not consider any pathway of exposure other than inhalation (e.g. diet, dermal, etc.) and the risk assessment should be evaluated in that context. | 18,957,992 |
Multipolar analysis of second-harmonic radiation from gold nanoparticles. | We present a multipolar tensor analysis of second-harmonic radiation from arrays of noncentrosymmetric L-shaped gold nanoparticles. Our approach is based on the fundamental differences in the radiative properties of electric dipoles and higher multipoles, which give rise to differences in the nonlinear response tensors for the reflected and transmitted second-harmonic signals. The results are analyzed by dividing the tensors into symmetric (dipolar) and antisymmetric (higher multipolar) parts between the two directions. The nonlinear response is found to be dominated by a tensor component, not resolved earlier [Phys. Rev. Lett. 98, 167403 (2007)], which is associated with chiral symmetry breaking of the sample and which also contains a strong multipolar contribution. The results are explained by a phenomenological model where asymmetrically-distributed defects on opposite sides of the particles give rise to dipolar and quadrupolar second-harmonic emission. | 18,958,000 |
Exploring the limits of single emitter detection in fluorescence and extinction. | We present an experimental comparison and a theoretical analysis of the signal-to-noise ratios in fluorescence and extinction spectroscopy of a single emitter. We show that because of its homodyne nature the extinction measurements can be advantageous if the emitter is weakly excited. Furthermore, we discuss the potential of this method for the detection and spectroscopy of weakly emitting systems such as rare earth ions. | 18,958,019 |
Trans-rectal ultrasound-coupled near-infrared optical tomography of the prostate, part I: simulation. | We investigate the feasibility of trans-rectal optical tomography of the prostate using an endo-rectal near-infrared (NIR) applicator that is to be integrated with a trans-rectal ultrasound (TRUS) probe. Integration with TRUS ensures accurate endo-rectal positioning of the NIR applicator and the utility of using TRUS spatial prior information to guide NIR image reconstruction. The prostate NIR image reconstruction is challenging even with the use of spatial prior owing to the anatomic complexity of the imaging domain. A hierarchical reconstruction algorithm is developed that implements cascaded initial-guesses for nested domains. This hierarchical image reconstruction method is then applied to evaluating a number of NIR applicator designs for integration with a sagittal TRUS transducer. A NIR applicator configuration feasible for instrumentation development is proposed that contains one linear array of optodes on each lateral side of the sagittal TRUS transducer. The performance of this NIR applicator is characterized for the recovery of single tumor mimicking lesion as well as dual targets in the prostate. The results suggest a strong feasibility of transrectal prostate imaging by use of the endo-rectal NIR/US probe. | 18,958,030 |
Advancing multifocal nonlinear microscopy: development and application of a novel multibeam Yb:KGd(WO4)2 oscillator. | We present a novel Yb:KGd(WO(4))(2) oscillator design that generates six beams of temporally delayed, 253 fs, 11 nJ pulses. This allows multifocal nonlinear microscopy to be performed without the need for complicated optical multiplexers. We demonstrate our design with twelve simultaneously acquired two-photon, second-harmonic and/or third-harmonic images generated from six laterally separated foci. | 18,958,037 |
A comparative study of noisy signal evolution in 2R all-optical regenerators with normal and anomalous average dispersions using an accelerated Multicanonical Monte Carlo method. | In [Opt. Express 15, 10061 (2007)] we proposed a new regime of multichannel all-optical regeneration that required anomalous average dispersion. This regime is superior to the previously studied normal-dispersion regime when signal distortions are deterministic in their temporal shape. However, there was a concern that the regenerator with anomalous average dispersion may be prone to noise amplification via modulational instability. Here, we show that this, in general, is not the case. Moreover, in the range of input powers that is of interest for multichannel regeneration, the device with anomalous average dispersion may even provide less noise amplification than the one with normal dispersion. These results are obtained with an improved version of the parallelized modification of the Multicanonical Monte Carlo method proposed in [IEEE J. Sel. Topics Quantum Electron. 14, 599 (2008)]. | 18,958,052 |
Two-photon-induced excited-state nonlinearities. | We report a theoretical investigation of laser-pulse-duration dependence of excited-state nonlinearities induced by two-photon absorption (2PA). We investigate the spatiotemporal characteristics of the transmitted pulses caused by 2PA-induced excited-state absorption, which strongly depends on laser pulse duration. By taking into account 2PA cross-section, excited-state photophysical properties, as well as laser pulse duration, we quantitatively determine the effective fifth-order nonlinearities caused by excited-state absorption and refraction. The results are capable of predicting the magnitude of 2PA-induced excited-state nonlinearities on the time scales where laser pulse duration is less than or comparable to the lifetime of 2PA-induced excited states. We also develop Z-scan theories for quickly yet unambiguously estimation of 2PA coefficient, third-order nonlinear refraction index, and excited-state absorption and refraction cross-sections. | 18,958,055 |
Application of structured illumination for multiple scattering suppression in planar laser imaging of dense sprays. | A novel approach to reduce the multiple light scattering contribution in planar laser images of atomizing sprays is reported. This new technique, named Structured Laser Illumination Planar Imaging (SLIPI), has been demonstrated in the dense region of a hollow-cone water spray generated in ambient air at 50 bars injection pressure. The idea is based on using an incident laser sheet which is spatially modulated along the vertical direction. By properly shifting the spatial phase of the modulation and using post-processing of the successive recorded images, the blurring effects from multiple light scattering can be mitigated. Since hollow-cone sprays have a known inner structure in the central region, the efficiency of the method could be evaluated. We demonstrate, for the case of averaged images, that an unwanted contribution of 44% of the detected light intensity can be removed. The suppression of this diffuse light enables an increase from 55% to 80% in image contrast. Such an improvement allows a more accurate description of the near-field region and of the spray interior. The possibility of extracting instantaneous flow motion is also shown, here, for a dilute flow of water droplets. These results indicate promising applications of the technique to denser two-phase flows such as air-blast atomizer and diesel sprays. | 18,958,069 |
An analysis of heterodyne signals in apertureless scanning near-field optical microscopy. | This study constructs interference-based model of the apertureless scanning near-field optical microscopy (A-SNOM) heterodyne detection signal which takes account of both the tip enhancement phenomena and the tip reflective background electric field. The analytical model not only provides a meaningful explanation of the image artifacts and errors, but also suggests methods for reducing these effects. It is shown that the detection signal obtained in the heterodyne A-SNOM method has a significantly higher signal-to-background (S/B) ratio than in the homodyne method. It is also shown that the S/B ratio increases as the wavelength of the illuminating light source is increased or the incident angle is reduced. Finally, an inspection reveals two fundamental phenomena which may potentially be exploited to obtain further significant improvements, namely (1) the modulation depth parameter has certain specific values greater than 1; and (2) the AFM tip apparatus using a ramp function. | 18,958,078 |
All-optical retrieval of the global phase for two-dimensional Fourier-transform spectroscopy. | A combination of spatial interference patterns and spectral interferometry are used to find the global phase for non-collinear two-dimensional Fourier-transform (2DFT) spectra. Results are compared with those using the spectrally resolved transient absorption (STRA) method to find the global phase when excitation is with co-linear polarization. Additionally cross-linear polarized 2DFT spectra are correctly "phased" using the all-optical technique, where the SRTA is not applicable. | 18,958,080 |
Photonic crystal with multiple-hole defect for sensor applications. | A photonic crystal defect consisting of several subwavelength holes was investigated as a means to increase the surface area of the defect region without compromising the quality factor of the structure. Finite-difference time-domain calculations were performed to determine the relationships between the size of the multi-hole defect (MHD) region, resonance frequency, quality factor, and refractive index of the defect holes. The advantage of using the MHD for sensing applications is demonstrated through a comparison with a single hole defect (SHD) photonic crystal structure. Assuming the same monolayer thickness of biomaterial coats the defect hole walls of the MHD and SHD, the MHD has a three times larger change in resonance frequency and two times larger quality factor. | 18,958,096 |
Realtime photoacoustic microscopy of murine cardiovascular dynamics. | Non-invasive visualization of cardiovascular dynamics in small animals is challenging due to their rapid heart-rates. We present a realtime photoacoustic imaging system consisting of a 30-MHz ultrasound array transducer, receive electronics, a high-repetition-rate laser, and a multicore-computer, and demonstrate its ability to image optically-absorbing structures of the beating hearts of young athymic nude mice at rates of approximately 50 frames per second with 100 microm x 25 microm spatial resolution. To our knowledge this is the first report of realtime photoacoustic imaging of physiological dynamics. | 18,958,134 |
Two distinct modes of hypoosmotic medium-induced release of excitatory amino acids and taurine in the rat brain in vivo. | A variety of physiological and pathological factors induce cellular swelling in the brain. Changes in cell volume activate several types of ion channels, which mediate the release of inorganic and organic osmolytes and allow for compensatory cell volume decrease. Volume-regulated anion channels (VRAC) are thought to be responsible for the release of some of organic osmolytes, including the excitatory neurotransmitters glutamate and aspartate. In the present study, we compared the in vivo properties of the swelling-activated release of glutamate, aspartate, and another major brain osmolyte taurine. Cell swelling was induced by perfusion of hypoosmotic (low [NaCl]) medium via a microdialysis probe placed in the rat cortex. The hypoosmotic medium produced several-fold increases in the extracellular levels of glutamate, aspartate and taurine. However, the release of the excitatory amino acids differed from the release of taurine in several respects including: (i) kinetic properties, (ii) sensitivity to isoosmotic changes in [NaCl], and (iii) sensitivity to hydrogen peroxide, which is known to modulate VRAC. Consistent with the involvement of VRAC, hypoosmotic medium-induced release of the excitatory amino acids was inhibited by the anion channel blocker DNDS, but not by the glutamate transporter inhibitor TBOA or Cd2+, which inhibits exocytosis. In order to elucidate the mechanisms contributing to taurine release, we studied its release properties in cultured astrocytes and cortical synaptosomes. Similarities between the results obtained in vivo and in synaptosomes suggest that the swelling-activated release of taurine in vivo may be of neuronal origin. Taken together, our findings indicate that different transport mechanisms and/or distinct cellular sources mediate hypoosmotic medium-induced release of the excitatory amino acids and taurine in vivo. | 18,958,155 |
In vitro identification and characterization of CD133(pos) cancer stem-like cells in anaplastic thyroid carcinoma cell lines. | Recent publications suggest that neoplastic initiation and growth are dependent on a small subset of cells, termed cancer stem cells (CSCs). Anaplastic Thyroid Carcinoma (ATC) is a very aggressive solid tumor with poor prognosis, characterized by high dedifferentiation. The existence of CSCs might account for the heterogeneity of ATC lesions. CD133 has been identified as a stem cell marker for normal and cancerous tissues, although its biological function remains unknown. ATC cell lines ARO, KAT-4, KAT-18 and FRO were analyzed for CD133 expression. Flow cytometry showed CD133(pos) cells only in ARO and KAT-4 (64+/-9% and 57+/-12%, respectively). These data were confirmed by qRT-PCR and immunocytochemistry. ARO and KAT-4 were also positive for fetal marker oncofetal fibronectin and negative for thyrocyte-specific differentiating markers thyroglobulin, thyroperoxidase and sodium/iodide symporter. Sorted ARO/CD133(pos) cells exhibited higher proliferation, self-renewal, colony-forming ability in comparison with ARO/CD133(neg). Furthermore, ARO/CD133(pos) showed levels of thyroid transcription factor TTF-1 similar to the fetal thyroid cell line TAD-2, while the expression in ARO/CD133(neg) was negligible. The expression of the stem cell marker OCT-4 detected by RT-PCR and flow cytometry was markedly higher in ARO/CD133(pos) in comparison to ARO/CD133(neg) cells. The stem cell markers c-KIT and THY-1 were negative. Sensitivity to chemotherapy agents was investigated, showing remarkable resistance to chemotherapy-induced apoptosis in ARO/CD133(pos) when compared with ARO/CD133(neg) cells. We describe CD133(pos) cells in ATC cell lines. ARO/CD133(pos) cells exhibit stem cell-like features--such as high proliferation, self-renewal ability, expression of OCT-4--and are characterized by higher resistance to chemotherapy. The simultaneous positivity for thyroid specific factor TTF-1 and onfFN suggest they might represent putative thyroid cancer stem-like cells. Our in vitro findings might provide new insights for novel therapeutic approaches. | 18,958,156 |
Stage- and gender-specific proteomic analysis of Brugia malayi excretory-secretory products. | While we lack a complete understanding of the molecular mechanisms by which parasites establish and achieve protection from host immune responses, it is accepted that many of these processes are mediated by products, primarily proteins, released from the parasite. Parasitic nematodes occur in different life stages and anatomical compartments within the host. Little is known about the composition and variability of products released at different developmental stages and their contribution to parasite survival and progression of the infection. To gain a deeper understanding on these aspects, we collected and analyzed through 1D-SDS PAGE and LC-MS/MS the Excretory-Secretory Products (ESP) of adult female, adult male and microfilariae of the filarial nematode Brugia malayi, one of the etiological agents of human lymphatic filariasis. This proteomic analysis led to the identification of 228 proteins. The list includes 76 proteins with unknown function as well as also proteins with potential immunoregulatory properties, such as protease inhibitors, cytokine homologues and carbohydrate-binding proteins. Larval and adult ESP differed in composition. Only 32 proteins were shared between all three stages/genders. Consistent with this observation, different gene ontology profiles were associated with the different ESP. A comparative analysis of the proteins released in vitro by different forms of a parasitic nematode dwelling in the same host is presented. The catalog of secreted proteins reflects different stage- and gender-specific related processes and different strategies of immune evasion, providing valuable insights on the contribution of each form of the parasite for establishing the host-parasite interaction. | 18,958,170 |
Coincidence between transcriptome analyses on different microarray platforms using a parametric framework. | A parametric framework for the analysis of transcriptome data is demonstrated to yield coincident results when applied to data acquired using two different microarray platforms. Microarrays are widely employed to acquire transcriptome information, and several platforms of chips are currently in use. However, discrepancies among studies are frequently reported, particularly among those performed using different platforms, casting doubt on the reliability of collected data. The inconsistency among observations can be largely attributed to differences among the analytical frameworks employed for data analysis. The existing frameworks are based on different philosophies and yield different results, but all involve normalization against a standard determined from the data to be analyzed. In the present study, a parametric framework based on a strict model for normalization is applied to data acquired using several slide-glass-type chips and GeneChip. The model is based on a common statistical characteristic of microarray data, and each set of chip data is normalized on the basis of a linear relationship with this model. In the proposed framework, the expressional changes observed and genes selected are coincident between platforms, achieving superior universality of data compared to other frameworks. | 18,958,174 |
Progestin receptor-mediated reduction of anxiety-like behavior in male rats. | It is well known progesterone can have anxiolytic-like effects in animals in a number of different behavioral testing paradigms. Although progesterone is known to influence physiology and behavior by binding to classical intracellular progestin receptors, progesterone's anxiety reducing effects have solely been attributed to its rapid non-genomic effects at the GABA A receptor. This modulation occurs following the bioconversion of progesterone to allopregnanolone. Seemingly paradoxical results from some studies suggested that the function of progesterone to reduce anxiety-like behavior may not be entirely clear; therefore, we hypothesized that progesterone might also act upon progestin receptors to regulate anxiety. To test this, we examined the anxiolytic-like effects of progesterone in male rats using the elevated plus maze, a validated test of anxiety, and the light/dark chamber in the presence or absence of a progestin receptor antagonist, RU 486. Here we present evidence suggesting that the anxiolytic-like effects of progesterone in male rats can be mediated, in part, by progestin receptors, as these effects are blocked by prior treatment with a progestin receptor antagonist. This indicates that progesterone can act upon progestin receptors to regulate anxiety-like behavior in the male rat brain. | 18,958,180 |
CRF1 receptor activation increases the response of neurons in the basolateral nucleus of the amygdala to afferent stimulation. | The basolateral nucleus (BLA) of the amygdala contributes to the consolidation of memories for emotional or stressful events. The nucleus contains a high density of CRF1 receptors that are activated by corticotropin-releasing factor (CRF). Modulation of the excitability of neurons in the BLA by CRF may regulate the immediate response to stressful events and the formation of associated memories. In the present study, CRF was found to increase the amplitude of field potentials recorded in the BLA following excitatory afferent stimulation, in vitro. The increase was mediated by CRF1 receptors, since it could be blocked by the selective, non-peptide antagonists, NBI30775 and NBI35583, but not by the CRF2-selective antagonist, astressin 2B. Furthermore, the CRF2-selective agonist, urocortin II had no effect on field potential amplitude. The increase induced by CRF was long-lasting, could not be reversed by subsequent administration of NBI35583, and required the activation of protein kinase C. This effect of CRF in the BLA may be important for increasing the salience of aversive stimuli under stressful conditions, and for enhancing the consolidation of associated memories. The results provide further justification for studying the efficacy of selective antagonists of the CRF1 receptor to reduce memory formation linked to emotional or traumatic events, and suggest that these compounds might be useful as prophylactic treatments for stress-related illnesses such as post-traumatic stress disorder. | 18,958,192 |
Response inhibition is linked to emotional devaluation: behavioural and electrophysiological evidence. | To study links between the inhibition of motor responses and emotional evaluation, we combined electrophysiological measures of prefrontal response inhibition with behavioural measures of affective evaluation. Participants first performed a Go-Nogo task in response to Asian and Caucasian faces (with race determining their Go or Nogo status), followed by a trustworthiness rating for each face. Faces previously seen as Nogo stimuli were rated as less trustworthy than previous Go stimuli. To study links between the efficiency of response inhibition in the Go-Nogo task and subsequent emotional evaluations, the Nogo N2 component was quantified separately for faces that were later judged to be high versus low in trustworthiness. Nogo N2 amplitudes were larger in response to low-rated as compared to high-rated faces, demonstrating that trial-by-trial variations in the efficiency of response inhibition triggered by Nogo faces, as measured by the Nogo N2 component, co-vary with their subsequent affective evaluation. These results suggest close links between inhibitory processes in top-down motor control and emotional responses. | 18,958,213 |
Sequential activation of human oculomotor centers during planning of visually-guided eye movements: a combined fMRI-MEG study. | We used magneto-encephalography (MEG) to measure visually evoked activity in healthy volunteers performing saccadic eye movements to visual targets. The neuromagnetic activity was analyzed from regions of cortical activation identified in separate functional magnetic resonance imaging (fMRI) studies. The latency of visual responses significantly increased from the Middle Temporal region (MT+) to the Intraparietal Sulcus (IPS) to the Frontal Eye Field (FEF), and their amplitude was greater in the hemisphere contralateral to the visual target. Trial-to-trial variability of oculomotor reaction times correlated with visual response latency across cortical areas. These results support a feedforward recruitment of oculomotor cortical centers by visual information, and a model in which behavioral variability depends on variability at different neural stages of processing. | 18,958,215 |
No disillusions in auditory extinction: perceiving a melody comprised of unperceived notes. | The formation of coherent percepts requires grouping together spatio-temporally disparate sensory inputs. Two major questions arise: (1) is awareness necessary for this process; and (2) can non-conscious elements of the sensory input be grouped into a conscious percept? To address this question, we tested two patients suffering from severe left auditory extinction following right hemisphere damage. In extinction, patients are unaware of the presence of left side stimuli when they are presented simultaneously with right side stimuli. We used the 'scale illusion' to test whether extinguished tones on the left can be incorporated into the content of conscious awareness. In the scale illusion, healthy listeners obtain the illusion of distinct melodies, which are the result of grouping of information from both ears into illusory auditory streams. We show that the two patients were susceptible to the scale illusion while being consciously unaware of the stimuli presented on their left. This suggests that awareness is not necessary for auditory grouping and non-conscious elements can be incorporated into a conscious percept. | 18,958,228 |
Conditioned reinforcement can be mediated by either outcome-specific or general affective representations. | Conditioned reinforcers are Pavlovian cues that support the acquisition and maintenance of new instrumental responses. Responding on the basis of conditioned rather than primary reinforcers is a pervasive part of modern life, yet we have a remarkably limited understanding of what underlying associative information is triggered by these cues to guide responding. Specifically, it is not certain whether conditioned reinforcers are effective because they evoke representations of specific outcomes or because they trigger general affective states that are independent of any specific outcome. This question has important implications for how different brain circuits might be involved in conditioned reinforcement. Here, we use specialized Pavlovian training procedures, reinforcer devaluation and transreinforcer blocking, to create cues that were biased to preferentially evoke either devaluation-insensitive, general affect representations or, devaluation-sensitive, outcome-specific representations. Subsequently, these cues, along with normally conditioned control cues, were presented contingent on lever pressing. We found that intact rats learned to lever press for either the outcome or the affect cues to the same extent as for a normally conditioned cue. These results demonstrate that conditioned reinforcers can guide responding through either type of associative information. Interestingly, conditioned reinforcement was abolished in rats with basolateral amygdala lesions. Consistent with the extant literature, this result suggests a general role for basolateral amygdala in conditioned reinforcement. The implications of these data, combined with recent reports from our laboratory of a more specialized role of orbitofrontal cortex in conditioned reinforcement, will be discussed. | 18,958,230 |
Cortical activity influences geniculocortical spike efficacy in the macaque monkey. | Thalamocortical communication is a dynamic process influenced by both presynaptic and postsynaptic mechanisms. In this study, we recorded single-unit responses from cortical neurons that received direct input from the lateral geniculate nucleus (LGN) to address the question of whether prior patterns of cortical activity affect the ability of LGN inputs to drive cortical responses. By examining the ongoing activity that preceded the arrival of electrically evoked spikes from the LGN, we identified a number of activity patterns that were predictive of suprathreshold communication. Namely, cortical neurons were more likely to respond to LGN stimulation when their activity levels increased to 30-40Hz and/or their activity displayed rhythmic patterns (30 ms intervals) with increased power in the gamma frequency band. Cortical neurons were also more likely to respond to LGN stimulation when their activity increased 30-40 ms prior to stimulation, suggesting that the phase of gamma activity also contributes to geniculocortical communication. Based on these results, we conclude that ongoing activity in the cortex is not random, but rather organized in a manner that can influence the dynamics of thalamocortical communication. | 18,958,231 |
Multisensory integration produces an initial response enhancement. | The brain has evolved the ability to integrate information across the senses in order to improve the detection and disambiguation of biologically significant events. This multisensory synthesis of information leads to faster (and more accurate) behavioral responses, yet the underlying neural mechanisms by which these responses are speeded are as yet unclear. The aim of these experiments was to evaluate the temporal properties of multisensory enhancement in the physiological responses of neurons in the superior colliculus (SC). Of specific interest was the temporal evolution of their responses to individual modality-specific stimuli as well as to cross-modal combinations of these stimuli. The results demonstrate that cross-modal stimuli typically elicit faster, more robust, and more reliable physiological responses than do their modality-specific component stimuli. Response measures sensitive to the time domain showed that these multisensory responses were enhanced from their very onset, and that the acceleration of the enhancement was greatest within the first 40ms (or 50% of the response). The latter half of the multisensory response was typically only as robust and informative as predicted by a linear combination of the unisensory component responses. These results may reveal some of the key physiological changes underlying many of the SC-mediated behavioral benefits of multisensory integration. | 18,958,232 |
Category-specific responses to faces and objects in primate auditory cortex. | Auditory and visual signals often occur together, and the two sensory channels are known to influence each other to facilitate perception. The neural basis of this integration is not well understood, although other forms of multisensory influences have been shown to occur at surprisingly early stages of processing in cortex. Primary visual cortex neurons can show frequency-tuning to auditory stimuli, and auditory cortex responds selectively to certain somatosensory stimuli, supporting the possibility that complex visual signals may modulate early stages of auditory processing. To elucidate which auditory regions, if any, are responsive to complex visual stimuli, we recorded from auditory cortex and the superior temporal sulcus while presenting visual stimuli consisting of various objects, neutral faces, and facial expressions generated during vocalization. Both objects and conspecific faces elicited robust field potential responses in auditory cortex sites, but the responses varied by category: both neutral and vocalizing faces had a highly consistent negative component (N100) followed by a broader positive component (P180) whereas object responses were more variable in time and shape, but could be discriminated consistently from the responses to faces. The face response did not vary within the face category, i.e., for expressive vs. neutral face stimuli. The presence of responses for both objects and neutral faces suggests that auditory cortex receives highly informative visual input that is not restricted to those stimuli associated with auditory components. These results reveal selectivity for complex visual stimuli in a brain region conventionally described as non-visual "unisensory" cortex. | 18,958,243 |
Associative and non-associative plasticity in kenyon cells of the honeybee mushroom body. | The insect mushroom bodies are higher-order brain centers and critical for odor learning. We investigated experience dependent plasticity of their intrinsic neurons, the Kenyon cells (KCs). Using calcium imaging, we recorded KC responses and investigated non-associative plasticity by applying repeated odor stimuli. Associative plasticity was examined by performing appetitive odor learning experiments. Olfactory, gustatory and tactile antennal stimuli evoked phasic calcium transients in sparse ensembles of responding KCs. Repeated stimulation with an odor led to a decrease in KCs' response strength. The pairing of an odor (conditioned stimulus, CS) with a sucrose reward (unconditioned stimulus) induced a prolongation of KC responses. After conditioning, KC responses to a rewarded odor (CS+) recovered from repetition-induced decrease, while the responses to a non-rewarded odor (CS-) decreased further. The spatio-temporal pattern of activated KCs changed for both odors when compared with the response before conditioning but the change was stronger for the CS-. These results demonstrate that KC responses are subject to non-associative plasticity during odor repetition and undergo associative plasticity after appetitive odor learning. | 18,958,247 |
Spontaneous coronary artery dissection: current insights and therapy. | Spontaneous coronary artery dissection (SCAD) is a very rare cause of acute coronary syndromes in young otherwise healthy patients with a striking predilection for the female gender. The pathological mechanism has not been fully clarified yet. However, several diseases and conditions have been associated with SCAD, such as atherosclerosis, connective tissue disorders and the peripartum episode. In this paper we present a review of the literature, discussing the possible mechanisms for SCAD, therapeutic options and prognosis. The review is illustrated with two SCAD patients who had a recurrence of a spontaneous dissection in another artery within a few days after the initial event. Because of the susceptibility to recurrent spontaneous dissections we propose at least one week of observation in hospital. Further, we will elaborate on the possible conservative and invasive treatment strategies in the acute phase of SCAD. Primary percutaneous coronary intervention remains the reperfusion strategy of choice; however, in small and medium-sized arteries with normalised flow conservative treatment is defendable. In addition, after the acute phase evaluation of possible underlying diseases is necessary, because it affects further treatment. (Neth Heart J 2008;16:344-9.). | 18,958,258 |
Heaven can wait - or down to earth in real time: Near-death experience revisited. | Near-death experience (NDE) is an intriguing phenomenon that invites more questions than answers. Hitherto emphasis has been laid on apparent similarities in accounts of NDE to prove a supernatural origin while in fact unique differences besides gross similarities support a neurophysiological explanation. A teleological approach is suggested to explain the neuroprotective strategies involved and accordingly a forme fruste of the biological concept of hibernation is put forward as an unifying hypothesis for clarification. (Neth Heart J 2008;16:359-62.). | 18,958,261 |
Acquisition of growth-inhibitory antibodies against blood-stage Plasmodium falciparum. | Antibodies that inhibit the growth of blood-stage Plasmodium falciparum may play an important role in acquired and vaccine-induced immunity in humans. However, the acquisition and activity of these antibodies is not well understood. We tested dialysed serum and purified immunoglobulins from Kenyan children and adults for inhibition of P. falciparum blood-stage growth in vitro using different parasite lines. Serum antibodies were measured by ELISA to blood-stage parasite antigens, extracted from P. falciparum schizonts, and to recombinant merozoite surface protein 1 (42 kDa C-terminal fragment, MSP1-42). Antibodies to blood-stage antigens present in schizont protein extract and to recombinant MSP1-42 significantly increased with age and were highly correlated. In contrast, growth-inhibitory activity was not strongly associated with age and tended to decline marginally with increasing age and exposure, with young children demonstrating the highest inhibitory activity. Comparison of growth-inhibitory activity among samples collected from the same population at different time points suggested that malaria transmission intensity influenced the level of growth-inhibitory antibodies. Antibodies to recombinant MSP1-42 were not associated with growth inhibition and high immunoglobulin G levels were poorly predictive of inhibitory activity. The level of inhibitory activity against different isolates varied. Children can acquire growth-inhibitory antibodies at a young age, but once they are acquired they do not appear to be boosted by on-going exposure. Inhibitory antibodies may play a role in protection from early childhood malaria. | 18,958,278 |
Roadless wilderness area determines forest elephant movements in the Congo Basin. | A dramatic expansion of road building is underway in the Congo Basin fuelled by private enterprise, international aid, and government aspirations. Among the great wilderness areas on earth, the Congo Basin is outstanding for its high biodiversity, particularly mobile megafauna including forest elephants (Loxodonta africana cyclotis). The abundance of many mammal species in the Basin increases with distance from roads due to hunting pressure, but the impacts of road proliferation on the movements of individuals are unknown. We investigated the ranging behaviour of forest elephants in relation to roads and roadless wilderness by fitting GPS telemetry collars onto a sample of 28 forest elephants living in six priority conservation areas. We show that the size of roadless wilderness is a strong determinant of home range size in this species. Though our study sites included the largest wilderness areas in central African forests, none of 4 home range metrics we calculated, including core area, tended toward an asymptote with increasing wilderness size, suggesting that uninhibited ranging in forest elephants no longer exists. Furthermore we show that roads outside protected areas which are not protected from hunting are a formidable barrier to movement while roads inside protected areas are not. Only 1 elephant from our sample crossed an unprotected road. During crossings her mean speed increased 14-fold compared to normal movements. Forest elephants are increasingly confined and constrained by roads across the Congo Basin which is reducing effective habitat availability and isolating populations, significantly threatening long term conservation efforts. If the current road development trajectory continues, forest wildernesses and the forest elephants they contain will collapse. | 18,958,284 |
Taurine suppresses the spread of cell death in electrically coupled RPE cells. | To determine whether taurine exerts a protective effect on retinal pigment epithelium (RPE) cells exposed to a cytotoxic agent, cytochrome C (cyC), shown previously to induce apoptosis and produce cell death in electrically coupled neighboring cells. Monolayer cultures of confluent human RPE (ARPE-19) cells, which express gap-junctional proteins, were incubated in culture medium with or without taurine. After scrape loading cyC into the cells, we assayed these cells for caspase 3 activity and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining to determine the spread of apoptosis. We found that cyC, too large a molecule to traverse gap junctional channels, produced apoptosis in cells injured by the scrape as well as those distant from the site of the scrape, presumably by the intercellular transmission of a toxic agent through the gap junctions that couple these cells. Incubation in taurine, or the gap-junction blocker, octanol, before application of cyC, reduced significantly the fraction of cells undergoing apoptosis. Voltage clamp recordings from electrically coupled Xenopus oocytes transfected with Cx43 showed that junctional communication was unaffected by taurine. Our results indicate that taurine can serve to suppress cell death in RPE cells independent of any effect on gap junctions. We have considered various avenues by which taurine can exert its protective effect, but the precise mechanism involved under these experimental conditions has yet to be identified. | 18,958,305 |
A review of systematic reviews on pain interventions in hospitalized infants. | Hospitalized infants undergo multiple, repeated painful procedures. Despite continued efforts to prevent procedural pain and improve pain management, clinical guidelines and standards frequently do not reflect the highest quality evidence from systematic reviews. To critically appraise all systematic reviews on the effectiveness of procedural pain interventions in hospitalized infants. A structured review was conducted on published systematic reviews and meta-analyses of pharmacological and nonpharmacological interventions of acute procedural pain in hospitalized infants. Searches were completed in the Cochrane Database of Systematic Reviews, MEDLINE, EMBASE, CINAHL and PsycINFO. Two reviewers independently selected articles for review and rated the methodological quality of the included reviews using a validated seven-point quality assessment measure. Any discrepancies were resolved by a third reviewer. Of 1469 potential systematic reviews on interventions for painful procedures in hospitalized infants, 11 high-quality reviews were included in the analysis. Pharmacological interventions supported by research evidence included premedication for intubation, dorsal penile nerve block and EMLA (AstraZeneca Canada, Inc) for circumcision, and sucrose for single painful procedures. Non-nutritive sucking, swaddling, holding, touching, positioning, facilitative tucking, breast feeding and supplemental breast milk were nonpharmacological interventions supported for procedural pain. There is a growing number of high-quality reviews supporting procedural pain management in infants. Ongoing research of single, repeated and combined pharmacological and nonpharmacological interventions is required to provide the highest quality evidence to clinicians for decision-making on optimal pain management. | 18,958,314 |
Photoreduction of 2-methyl-1-nitro-9,10-anthraquinone in the presence of 1-phenylethanol. | The photoreactions of 1-nitro-9,10-anthraquinone (N1) and 2-methyl-1-nitro-9,10-anthraquinone (N2) were studied in benzene and acetonitrile in the presence of 1-phenylethanol. For N2, a short-lived 10 ns transient observed upon flash photolysis is attributed to a triplet state, which can be intercepted by 1-phenylethanol to form a monohydro radical of N2 and a spectroscopically not detectable donor-derived radical. The decay of radicals yields the corresponding nitroso compound and eventually 1-amino-2-methyl-9,10-anthraquinone (A2) as photoproduct. The final reduction step requires participation of the anthraquinone carbonyl groups. The yield of radicals and the quantum yield (Phi(NH(2))) of conversion to A2 are small in inert solvents and increase with the donor concentration, approaching Phi(NH(2)) = 0.2. No triplet state was observed in the flash photolysis of N1, but a N1-derived radical and 1-amino-9,10-anthraquinone (A1) as final products were found. Various mechanistic aspects of complete photoreduction of nitroarenes to aminoarenes are discussed. | 18,958,321 |
Chlorochromate ion as a catalyst for the photodegradation of chloroform by visible light. | Exposure of solutions of tetrabutylammonium chlorochromate in chloroform to UV or blue light causes decomposition of the chloroform and the buildup of HCl and peroxides in solution. The CrO(3)Cl(-) is converted during irradiation to CrO(2)Cl(2), which forms a suspension in the chloroform, and then to CrOCl(4)(-). CrO(2)Cl(2) does not by itself catalyze photodecomposition. The initial rate of HCl formation shows an apparently linear dependence on the incident light intensity and on the fraction of light absorbed by chlorochromate, but different values for the apparent quantum yield at 435 nm with high and low concentrations imply a nonlinear contribution to the rate. It is proposed that, at least initially, a cycle involving photoreduction of a Cr(vi) species and thermal reoxidation of Cr(v) by CCl(3)OOH produces radicals that initiate further decomposition. | 18,958,324 |
Characterization of new fluorescent labels for ultra-high resolution microscopy. | Photo-induced switching of dyes into dark, long-lived states, such as a triplet state, has recently gained increasing interest, as a means to achieve ultra-high optical resolution. Additionally, these long lived states are often highly environment-sensitive and their photodynamics can thus offer additional independent fluorescence-based information. However, although providing a useful mechanism for photo-induced switching, the triplet state often appears as a precursor state for photobleaching, which potentially can limit its usefulness. In this work, a set of rhodamine and pyronin dyes, modified by substitution of heavy atoms and nitrogen within or close to the central xanthene unit of the dyes, were investigated with respect to their triplet state dynamics and photostabilities, under conditions relevant for ultra-high resolution microscopy. Out of the dyes investigated, in particular the rhodamine and pyronin dyes with a sulfur atom replacing the central oxygen atom in the xanthene unit were found to meet the requirements for ultra-high resolution microscopy, combining a prominent triplet state yield with reasonable photostability. | 18,958,325 |
Radical cage effects: a method for measuring recombination efficiencies of secondary geminate radical cage pairs using pump-probe transient absorption methods. | A method is reported for measuring the recombination efficiency of secondary geminate radical cage pairs. The procedure involves measuring the recombination efficiency for primary geminate recombination (F(c1)) using pump-probe laser methods and measuring the "apparent" (or net) recombination efficiency (F(cP)) for all geminate pairs (primary and secondary) using steady-state irradiation methods. A mathematical relationship between F(cP), F(c1), and F(c2) (where F(c2) is the recombination efficiency for secondary geminate recombination) is derived and demonstrated using the photolysis reactions of the [(CpR)Mo(CO)(3)](2) molecules, where CpR = eta(5)-C(5)H(4)CH(3) and eta(5)-C(5)H(4)(CH(2))(2)C(O)NCH(3)(CH(2))(n)CH(3) (n = 3, 8, 13, 18). As an example of the results obtained using the new method, it was found that F(c1) = 0.43 and F(c2) = 0.68 for the molecule with CpR = eta(5)-C(5)H(4)CH(2)CH(2)N(CH(3))C(O)(CH(2))(18)CH(3). The value of F(c2) decreased as the side-chain on the Cp ring got shorter; F(c2) is equal to 0.0 for the molecules with n = 3 and for CpR = eta(5)-C(5)H(4)CH(3). It is hypothesized that a longer side-chain prevents facile diffusion of the radicals out of the secondary cage, whereas the smaller side-chains permit more facile diffusion apart of the radicals. A general conclusion is that the reactions of large radicals in particular may be especially impacted by secondary geminate cage recombination. | 18,958,326 |
[Backpain and haemophilia]. | A literature research for back pain in hemophilia (1990-2007) revealed only five papers! They all had lumbar or sciatic pain due to hematoma. All symptoms responded to factor VIII replacement. A similar research for a normal population showed hundreds of papers with a lifetime prevalence of 80% for back pain. A survey of 49 patient with hemophilia showed similar results. 70% had experienced back pain before. The reported pain of 40 to 70 on a visual analog scale was significant. 40% reported that the back pain would be more limiting than the pain associated with hemophilia. The hemophilic patient has learned to cope! The treatment of back pain will be of growing importance for hemophilia centers while the typical complaints of hemophilic symptoms will decrease due to better treatment protocols. | 18,958,339 |
Enhanced thrombin generation in plasma of severe thrombocytopenic patients due to rFVIIa. | RFVIIa-enhanced thrombin generation has been shown to be dependent on platelets. In previous work we have shown that addition of monocytes and rFVIIa to microparticle free plasma causes a distinct thrombin generation. The aim of our study has been to examine whether there is enough surface provided by microparticles in thrombocytopenic plasma to allow an effect of rFVIIa. Thrombin generation was measured in platelet rich plasma (PRP) and microparticle free plasma (MFP) of thrombocytopenic haemato-oncological patients with and without addition of rVIIa by means of calibrated automated thrombography. Microparticles were analyzed in PRP by FACS flow cytometry. Microparticle free plasma showed no thrombin generation with or without addition of rFVIIa. Addition of rFVIIa to PRP of thrombocytopenic patients led to a significant shortening of lag time and time to peak in thrombin generation, while ETP and peak remained unchanged. Our results show that even in plasma of severe thrombocytopenic patients enough surface may be provided by microparticles to allow an enhancement of thrombin generation by rFVIIa. | 18,958,344 |
Sperm nuclear histone H2B: correlation with sperm DNA denaturation and DNA stainability. | To examine the relationship between sperm DNA damage and sperm nuclear histone (H2B) staining. We evaluated sperm samples from 14 consecutive asthenoteratozoospermic infertile men and six consecutive fertile controls. Sperm nuclear histone (H2B) staining and sperm chromatin integrity (assessed by sperm chromatin structure assay and expressed using the percentage of (i) DNA fragmentation index [% DFI] and (ii) high DNA stainability [% HDS)]) were evaluated. Histone H2B immunocytochemistry demonstrated two nuclear staining patterns: (i) focal punctate staining; and (ii) diffuse staining. Infertile men had a higher mean percentage of spermatozoa exhibiting diffuse H2B staining than did fertile men (7.7% +/- 4.6% vs. 1.6% +/- 1.2%, respectively, P < 0.01). We observed significant relationships between the proportion of spermatozoa with diffuse nuclear histone staining and both sperm % DFI (r = 0.63, P < 0.01) and sperm %HDS (r = 0.63, P < 0.01). The data demonstrate that infertile men have a higher proportion of spermatozoa with diffuse histone H2B than do fertile men and suggest that sperm DNA damage might, at least in part, be due to abnormally high histone H2B levels. | 18,958,350 |
Postnatal roles of glial cell line-derived neurotrophic factor family members in nociceptors plasticity. | The neurotrophin and glial cell line-derived neurotrophic factor (GDNF) family of growth factors have been extensively studied because of their proven ability to regulate development of the peripheral nervous system. The neurotrophin family, which includes nerve growth factor (NGF), NT-3, NT4/5 and BDNF, is also known for its ability to regulate the function of adult sensory neurons. Until recently, little was known concerning the role of the GNDF-family (that includes GDNF, artemin, neurturin and persephin) in adult sensory neuron function. Here we describe recent data that indicates that the GDNF family can regulate sensory neuron function, that some of its members are elevated in inflammatory pain models and that application of these growth factors produces pain in vivo. Finally we discuss how these two families of growth factors may converge on a single membrane receptor, TRPV1, to produce long-lasting hyperalgesia. | 18,958,362 |
Australian pelvic floor questionnaire: a validated interviewer-administered pelvic floor questionnaire for routine clinic and research. | The aim of this study was to design and validate an interviewer-administered pelvic floor questionnaire that integrates bladder, bowel and sexual function, pelvic organ prolapse, severity, bothersomeness and condition-specific quality of life. Validation testing of the questionnaire was performed using data from 106 urogynaecological patients and a separately sampled community cohort of 49 women. Missing data did not exceed 2% for any question. It distinguished community and urogynaecological populations regarding pelvic floor dysfunction. The bladder domain correlated with the short version of the Urogenital Distress Inventory, bowel function with an established bowel questionnaire and prolapse symptoms with the International Continence Society prolapse quantification. Sexual function assessment reflected scores on the McCoy Female Sexuality Questionnaire. Cronbach's alpha coefficients were acceptable in all domains. Kappa coefficients of agreement for the test-retest analyses varied from 0.5 to 1.0. The interviewer-administered pelvic floor questionnaire assessed pelvic floor function in a reproducible and valid fashion in a typical urogynaecological clinic. | 18,958,382 |
Typical trigeminal neuralgia associated with brainstem white matter lesions on MRI in patients without criteria of multiple sclerosis. | Although compression of the trigeminal nerve by a vascular loop is thought to be the most common cause of trigeminal neuralgia (TN), other aetiologies, such as multiple sclerosis or brainstem infarction may be associated with this disorder. MRI may detect lesions different from vascular loop compression of the trigeminal nerve that may be related to TN. The pre-operative MRIs of 68 patients without the diagnosis of multiple sclerosis who were operated for typical TN between 1998 and 2003 were retrospectively reviewed Four of these showed hyperintense lesions in the pons on T2 MRI sequences. No patient had prior surgery. These four patients underwent different operations for the control of pain but in two of them only ablative procedures were effective Although it is uncertain whether the occurrence of TN in our patients may be attributed to the brainstem abnormalities seen on MRI, the presence of these lesions appears to be the most convincing explanation for the occurrence of pain. We believe that, in the presence of such imaging changes, a destructive procedure should be regarded as the elective surgical treatment in patients presenting with typical TN with or without apparent vascular loop compression of the trigeminal root. | 18,958,387 |
Intractable hiccups as a presenting symptom of Chiari I malformation. | Hiccups as the only presenting symptom in neurosurgical practice is uncommon. We report a case of a 22-year-old man who was evaluated for a 9-month history of intractable hiccups. He was diagnosed with a case of Chiari malformation type I. Surgical decompression improved the symptoms of the patient. The cause and pathogenesis of hiccups are discussed. Chiari malformation should be considered in patients with intractable hiccups, who are otherwise asymptomatic for any neurological problems. | 18,958,392 |
Interdisciplinarity and participatory approaches to environmental health: reflections from a workshop on social, economic and behavioural factors in the genesis and health impact of environmental hazards. | This paper reviews a workshop discussion postulated on the notion that social, economic and behavioural factors are responsible for the creation of environmental hazards and benefits that, in turn, can affect human health, with concomitant effects on future social well-being. The workshop case study centred on environmental health investigations, public engagement and partnership work undertaken following the death of two neighbouring children in Cheshire. Discussion included questions of causality and generalisability. It revealed how the attribution of responsibility for environmental damage to health is fraught with difficulties. It may often militate against an informed and open debate among interested parties, with concomitant implications for reducing the danger from environmental hazards. To improve communication, vocabulary needs to be free from jargon and acronyms, and differences in conceptual approach between different disciplines need to be better understood. The definition of the 'community' is itself far from clear-cut, yet questions of how to involve this community in intervention processes are important ones. The workshop identified a clear need for better, more considered forms of communication with communities and the public if fears are to be allayed, but recognised the additional costs that this would incur. | 18,958,398 |
Return to work after injury: a review of evidence regarding expectations and injury perceptions, and their influence on outcome. | Work disability after injury is a complex problem, and there remains a lack of clarity about what factors are most influential on whether or not someone will experience difficulty returning to work. Increasingly, expectations and injury perceptions are being explored as potential factors in work disability, because of their role in influencing behaviours. This paper reviewed the literature regarding how expectations (regarding injury recovery and return to work) and injury perceptions relate to return to work outcome. A wide range of electronic journal databases were searched, and identified articles were critically appraised to assess quality and relevance. Results were then synthesised and discussed in relation to the evidence available regarding the role of expectations and injury perceptions in return to work, and implications for practice and further research. Findings showed that evidence regarding to how both expectations and injury perceptions contribute to return to work outcome is limited. Some suggestions for application to practice are made. Methodological issues and key points to consider for future research are discussed. While in general little is known about how much expectations and injury perceptions influence return to work outcome, it is clear that the issue requires further investigation. Key limits to current knowledge result from inadequate methods of measuring expectation/s, lack of clear definitions of 'return to work outcome' and differences in timeframes and populations. Never-the-less, there is promising evidence to suggest that, in particular, pain catastrophizing research is warranted due to its correlation with outcome and amenability to change. | 18,958,407 |
On-line characterization of physiological state in poly(beta-hydroxybutyrate) production by Wautersia eutropha. | Culture fluorescence measurement technique has the potential for on-line characterization of metabolic status of fermentation processes. Many fluorophores present inside the living cells such as NADH + H+, tryptophan, pyridoxine, and riboflavin fluoresce at specific excitation and emission wavelength combinations. Since these key intracellular metabolites are involved in cell growth and metabolism, their concentration change at any time inside the cell could reflect the changes in cell metabolic activity. NADH + H+ spectrofluorometry was used for on-line characterization of physiological state during batch cultivation of poly-beta-hydroxybutyric acid (PHB) production by Wautersia eutropha. The culture fluorescence increased with an increase in the biomass concentration with time. A linear correlation between cell mass concentration and net NADH + H+ fluorescence was established during active growth phase (13 to 38 h) of batch cultivation. The rate of change of culture fluorescence (dF/dt) exhibited a gradual increase during the predominantly growth phase of batch cultivation (till 20 h). Thereafter, a sudden drop in the dF/dt rate and its leveling was recorded indicating major changes in culture metabolism status which synchronized with the start-up of accumulation of PHB. After 48 h, yet another decrease in the rate of change of fluorescence (dF/dt) was observed primarily due to severe substrate limitation in the reactor. On-line NADH + H+ fluorescence signal and its rate (dF/dt) could therefore be used to distinguish the growth, product formation, and nutrient depletion stage (the metabolic state marker) during the batch cultivation of W. eutropha. | 18,958,410 |
APE1/Ref-1 promotes the effect of angiotensin II on Ca2+ -activated K+ channel in human endothelial cells via suppression of NADPH oxidase. | The effects of angiotensin II (Ang II) on whole-cell large conductance Ca(2+)-activated K(+) (BK(Ca)) currents was investigated in control and Apurinic/apyrimidinic endonuclease1/redox factor 1 (APE1/Ref-1)-overexpressing human umbilical vein endothelial cells (HUVECs). Ang II blocked the BK(Ca) current in a dose-dependent fashion, and this inhibition was greater in APE1/Ref-1-overexpressing HUVECs than in control HUVECs (half-inhibition values of 102.81+/-9.54 nM and 11.34+/-0.39 nM in control and APE1/Ref-1-overexpressing HUVECs, respectively). Pretreatment with the NADPH oxidase inhibitor diphenyleneiodonium (DPI) or knock down of NADPH oxidase (p22 phox) using siRNA increased the inhibitory effect of Ang II on the BK(Ca) currents, similar to the effect of APE1/Ref-1 overexpression. In addition, application of Ang II increased the superoxide and hydrogen peroxide levels in the control HUVECs but not in APE1/Ref-1-overexpressing HUVECs. Furthermore, direct application of hydrogen peroxide increased BK(Ca) channel activity. Finally, the inhibitory effect of Ang II on the BK(Ca) current was blocked by an antagonist of the Ang II type 1 (AT(1)) receptor in both control and APE1/Ref-1-overexpressing HUVECs. From these results, we conclude that the inhibitory effect of Ang II on BK(Ca) channel function is NADPH oxidase-dependent and may be promoted by APE1/Ref-1. | 18,958,420 |
A new ferulic acid ester and other constituents from Dracocephalum peregrinum. | A new ferulic acid ester, 1'-methyl-2'-hydroxyethyl ferulate (1), together with methylcaffeate (2), 4-hydroxy cinnamic acid (3), ferulic acid (4), caffeic acid (5), diosmetin (6), luteolin (7), 5,3',4'-trihydroxy-3,7-dimethoxyflavone (8), eriodictyol (9), kaempferol (10), quercetin (11), acacetin-7-O-glcopyranoside (12), 4-(beta-glucopyranosyloxy) benzoic acid (13), luteolin-7-O-(6''-feruloyl) glucopyranoside (14), luteolin-7-O-glucopyranoside (15), kaempferide-3-O-rhamnopyranoside (16), quercitrin (17), kaempferol-3-O-glucopyranoside (18), prunasin (19), quercetin-7-O-glucopyranoside (20), quercetin-3-O-glucopyranoside (21), plantaginin (22), linarin (23), luteolin-7-O-rutinoside (24), and chlorogenic acid (25) were isolated from the aerial parts of Dacocephalum peregrinum. The structure of 1 was elucidated on the basis of spectroscopic and HR-ESI-MS analyses. In addition, compound 1 exhibited mild inhibitory effect on NO production in LPS-stimulated RAW264.7 cells. | 18,958,424 |
In vitro and in vivo evaluation of ranitidine hydrochloride loaded hollow microspheres in rabbits. | The objective of this investigation was to develop the hollow microspheres as a new dosage form of floating drug delivery systems with prolonged stomach retention time. Hollow microspheres containing ranitidine hydrochloride (RH) were prepared by a novel solvent diffusion-evaporation method using ethyl cellulose (EC) dissolved in a mixture of ethanol and ether (6:1.0, v/v). The yield and drug loading amount of hollow microspheres were 83.21+/-0.28% and 20.71+/-0.32%, respectively. The in vitro release profiles showed that the drug release rate decreased with increasing viscosity of EC and the diameter of hollow microspheres, while increased with the increase of RH/EC weight ratio. Hollow microspheres could prolong drug release time (approximately 24 h) and float over the simulate gastric fluid for more than 24 h. Pharmacokinetic analysis showed that the bioavailability from RH-hollow microspheres alone was about 3.0-times that of common RH gelatin capsules, and it was about 2.8-times that of the solid microspheres. These results demonstrated that RH hollow microspheres were capable of sustained delivery of the drug for longer period with increased bioavailability. | 18,958,430 |
[Gender differences in psychopharmacology]. | At least half of all patients with psychiatric disorders are female. Depressive disorders occur twice as often in women than in men. Despite the need for a gender-specific approach in treating psychiatric disorders, little is known about gender issues in psychopharmacology. It has been recognized that women respond better than men to serotonin-modulating substances but that this effect is reversed after menopause. Furthermore, women develop gynecological complications under medication with certain psychopharmacological agents which calls the use of these drugs into question. Side effects such as weight gain, hyperglycemia, cardiac arrhythmias, and sexual dysfunction also occur more frequently in women than in men. Pregnancy is a particularly sensitive aspect. The risk that a mother with a psychiatric disorder could relapse if the drug is discontinued has to be weighed against the risk of the child being born with an anomaly or developing prenatal complications. | 18,958,437 |
[A 47-year-old patient with longstanding nicotine abuse, increasing dyspnea on exertion and lower and peripheral lung predominant ground-glass opacities]. | The causal relationship between cigarette smoking and a number of interstitial lung diseases continues to evolve. These "smoking-related interstitial lung diseases" (SR-ILD) are a heterogeneous group of entities which have overlapping imaging findings and which can coexist. The presented case of a patient with smoking history and pulmonary ground-glass opacities demonstrates that thorough knowledge of the various manifestations of SR-ILD is essential for a confident diagnosis. | 18,958,443 |
Renal injury at first presentation as a predictor for poor outcome in severe paracetamol poisoning referred to a liver transplant unit. | Paracetamol poisoning remains a leading cause of morbidity and mortality. Identifying indices of poor prognosis at first presentation is key to both improving clinical care and determining targets for intervention. Renal failure is a feature of severe paracetamol poisoning. The aim of this study was to investigate the relationship between renal function (serum creatinine, Cr) at first hospital presentation and time of tertiary referral to outcomes in severe paracetamol poisoning. This was a retrospective cohort analysis of patients referred to the Scottish Liver Transplant Unit due to paracetamol poisoning between 1992 and 2004. The relation between degree of renal injury and outcomes, including worst prothrombin time, Kings College Hospital Criteria (KCHC) and death were examined. The effects of age, nature (single or multiple) and stated size of overdose, hepatic enzyme induction (gamma-glutamyl transpeptidase, GGT), degree of liver injury (aspartate aminotransferase, prothrombin time), blood pressure and renal injury were assessed. Data from 522 patients were included. Renal impairment (Cr >120 mmol/l) was present in 48.8% of patients with liver injury at time of first presentation. Creatinine at first admission predicted poorer outcome in terms of worse prothrombin time, KCHC and death (p < 0.001). Associated risk factors for renal dysfunction included later presentation, staggered ingestion, increased age, hypotension and elevated GGT at first admission. Creatinine at first admission appears to be a predictor of poor outcome in paracetamol overdose. A better understanding of mechanisms involved in causing renal dysfunction may offer potential therapeutic targets for improving outcome in this common poisoning. | 18,958,458 |
Unusual manifestations of astroblastoma: a radiologic-pathologic analysis. | Astroblastoma is a very rare primary glial tumor occurring in children and young adults that is almost exclusively supratentorial in location. We report an extremely unusual presentation of a densely calcified posterior fossa astroblastoma with disseminated spinal and supratentorial metastasis. The mass exhibited neoplastic bone formation, which has not been reported, although calcifications are commonly seen in astroblastomas. A companion case of a low-grade astroblastoma that demonstrated classic histologic features but nonspecific and atypical imaging findings is also included. These cases expand the imaging and pathologic spectrum of this controversial tumor that shows highly variable biologic behavior and is difficult to distinguish from ependymoma. | 18,958,463 |
Prognostic significance of p16/cdkn2a loss in pleural malignant mesotheliomas. | Homozygous deletion of p16/CDKN2A is the most common genetic abnormality in malignant mesotheliomas. The aim of this study was to determine prognostic significance of p16/CDKN2A loss in malignant pleural mesotheliomas (MPM) as defined by immunohistochemistry and fluorescence in situ hybridization (FISH). High-density tissue microarrays were constructed from archival formalin-fixed paraffin-embedded samples of 48 MPM. Long survival (LS) was defined as survival greater than 3 years from the time of diagnosis, and short survival was defined as less than 3 years from the time of diagnosis. Both loss of p16 protein expression by immunohistochemistry and homozygous deletion of p16 by FISH were associated with adverse prognosis. Female gender, positive p16 immunoexpression, and lack of p16/CDKN2A deletion significantly predicted the survival for the LS group. Statistical analysis showed a very strong correlation of immunohistochemistry and FISH data. Cases positive for p16 immunoexpression and negative for 9p21 deletion showed the best survival time. Our study is the first to demonstrate decreased frequency of homozygous deletion of 9p21 and loss of p16 immunoreactivity in pleural mesotheliomas from patients with long-term survival of greater than 3 years in contrast to patients with rapidly fatal mesotheliomas. A possible implementation of these tests into preoperative prognostication of MPM and therapeutic decisions should be considered. | 18,958,493 |
Structure-function analysis of the barley genome: the gene-rich region of chromosome 2HL. | A major gene-rich region on the end of the long arm of Triticeae group 2 chromosomes exhibits high recombination frequencies, making it an attractive region for positional cloning. Traits known to be controlled by this region include chasmogamy/cleistogamy, frost tolerance at flowering, grain yield, head architecture, and resistance to Fusarium head blight and rusts. To assist these cloning efforts, we constructed detailed genetic maps of barley chromosome 2H, including 61 polymerase chain reaction markers. Colinearity with rice occurred in eight distinct blocks, including five blocks in the terminal gene-rich region. Alignment of rice sequences from the junctions of colinear chromosome segments provided no evidence for the involvement of long (>2.5 kb) inverted repeats in generating inversions. However, reuse of some junction sequences in two or three separate evolutionary breakage/fusion events was implicated, suggesting the presence of fragile sites. Sequencing across 91 gene fragments totaling 107 kb from four barley genotypes revealed the highest single nucleotide substitution and insertion-deletion polymorphism levels in the terminal regions of the chromosome arms. The maps will assist in the isolation of genes from the chromosome 2L gene-rich region in barley and wheat by providing markers and accelerating the identification of the corresponding points in the rice genome sequence. | 18,958,509 |
The change in surgical practice from subtotal to near-total or total thyroidectomy in the treatment of patients with benign multinodular goiter. | Although total thyroidectomy is the procedure of choice in patients with thyroid carcinoma, this surgical approach has emerged as a surgical option to treat patients with benign multinodular goiter (BMNG), especially in endemically iodine-deficient regions. The aim of this study was to review our experience with patients with BMNG in an endemically iodine-deficient region treated by either subtotal or total/near-total thyroidectomy, and to document whether total or near-total thyroidectomy decreased the rate of completion thyroidectomy for incidentally diagnosed thyroid carcinoma in comparison to the patients with BMNG treated initially by subtotal thyroidectomy. Two thousand five hundred ninety-two patients with BMNG were included. There were 1695 bilateral subtotal thyroidectomies (group 1) and 1211 total or near-total thyroidectomies (group 2) for BMNG during this period. All patients were euthyroid and had no history of hyperthyroidism, radiation exposure, or familial thyroid carcinoma. Any patient with preoperative or perioperative suspicion of malignancy or hyperthyroidism was excluded. Bilateral subtotal thyroidectomy was performed in 1695 patients (58.3%) in group 1 and total or near-total thyroidectomy in 1211 patients (41.7%), in group 2, respectively. The incidence of incidental thyroid carcinoma was found to be 7.2% (n = 210/2906). Although the rate of permanent hypoparathyroidim and transient or permanent unilateral recurrent laryngeal nerve (RLN) palsy were not significantly different between the two groups, transient hypoparathyroidism was significantly higher in group 2 than in group 1 (8.4% vs. 1.42%; p < 0.001, odds ratio [OR] = 52.98). The incidence of thyroid carcinoma was significantly higher in group 2 (10.7%, n = 129/1211) than in group 1 (4.68%, n = 81/1695) (p < 0.001; OR = 39.1).Thirty-eight patients in group 1 (2.24%) underwent completion thyroidectomy, whereas completion thyroidectomy has been not indicated in group 2 (p = 0.007). Two of 38 patients (5.26%) had thyroid papillary microcarcinoma on their remnant thyroid tissue. The rate of recurrent goiter was 7.1% in group 1. The average time to recurrence in group 1 was 14.9 +/- 8.7 years. Six of 121 patients with recurrent disease (4.95%) has been operated on. Subtotal thyroidectomy resulted in a significantly higher rate of completion thyroidectomy for incidentally diagnosed thyroid carcinoma compared with total or near-total thyroidectomy in patients with BMNG. The extent of surgical resection had no significant effect on the rate of permanent complications. We recommend total or near-total thyroidectomy in BMNG to prevent recurrence and to eliminate the necessity for early completion thyroidectomy in case of a final diagnosis of thyroid carcinoma. | 18,958,517 |
Total parathyroidectomy without autotransplantation for secondary hyperparathyroidism. | To treat secondary hyperparathyroidism with subtotal parathyroidectomy or total parathyroidectomy with autotransplantation might cause the disease to recur because of growth of the parathyroid remnant or the autografts. The aim of the present study was to determinate an alternative surgical treatment for secondary hyperparathyroidism. Of 94 uremic patients, 44 (median age: 50.5 years; 33 women/11 men) were assigned to group A, patients who were not expected to receive kidney transplantation for various reasons and had total parathyroidectomy without autotransplantation; 50 (median age 46 years; 33 women/17 men) were assigned to group B, patients who had either total parathyroidectomy with autotransplantation or subtotal total parathyroidectomy with preservation of parathyroid tissue in situ. Parameters measured included demographics, perioperative and follow-up biochemistry tests, operative time, postoperative complications, length of hospital stay, patients' compliance with the postoperative calcium and 1,25 dihydroxy-viatmin D supplementation regimen, symptom relief, and presence of recurrence. Mean operative times were 103 and 122 min (P = 0.007); postoperative complication rates were 18.2% and 12.0% (P = 0.563); mean hospital stays were 6 and 9 days (P = 0.259); adequate patient compliance with the postoperative calcium and 1,25 dihydroxy-viatmin D regimens were 84.1% and 78.0%, respectively (P = 0.6); symptom relief rates were 88.6% and 80.0% (P = 0.277). Recurrence rates over 60 months in group A and group B were 4.5% and 18.0%, resectively (P = 0.028 by Kaplan-Meier analysis). Because of the lower recurrent rate and shorter operative time, total parathyroidectomy without autotransplantation may be an option for treating patients with symptomatic secondary hyperparathyroidism who are not expected to receive kidney transplantation. | 18,958,522 |
Adjuvant postoperative radiotherapy to the cervical lymph nodes in cutaneous melanoma: is there any benefit for high-risk patients? | The use of adjuvant radiotherapy after lymph node dissection for metastatic melanoma remains controversial. This study examined the effectiveness of adjuvant radiotherapy in controlling regional disease in high-risk patients. A total of 716 patients were identified from a large prospective database who underwent cervical lymph node surgery between 1990 and 2004. Patients with high-risk disease were offered radiotherapy (n = 129), and this group was compared with the group of patients who did not receive radiotherapy (n = 587) in the same period. Radiotherapy did not improve regional control in patients who had metastatic melanoma of the cervical lymph nodes (P = .2). There were 10% fewer regional recurrences in patients with extracapsular spread who received adjuvant radiotherapy, although this was not statistically significant (P = .34). Adjuvant radiotherapy conferred no overall survival benefit to patients with nodal metastases (P = .39). There was a statistically significant trend for worse survival with increasing nodal tumor burden that remained unchanged with adjuvant radiotherapy. This large, nonrandomized retrospective study found no evidence to support the use of adjuvant radiotherapy for high-risk melanoma. A multicenter randomized, controlled trial investigating this important clinical dilemma is advocated. | 18,958,539 |
Abdominal aortic aneurysm surgery for octogenarians. | To define the indications for abdominal aortic aneurysm (AAA) surgery in octogenarians. We reviewed septuagenarians and octogenarians with a nonspecific AAA diagnosed at our hospital between January, 1990 and June, 2006. Among a total 628 patients seen, 306 were in their 70s (group A) and 108 were in their 80s or older (group B). The mortality rate associated with elective surgery was 1.9% in group A and 7.0% in group B. Of the survivors, 12 (5.7%) of 210 in group A and 8 (15.1%) of 53 in group B died within 2 years. Of the patients who did not undergo surgery, 8 of 53 in group A and 8 of 31 in group B had AAAs greater than 6 cm in diameter. The rupture-free rates of AAAs greater than 6 cm in diameter were 64% at 1 year and 0% at 4 years in group A, and 88% at 1 year and 26% at 3 years in group B. The rupture-free rates of AAAs smaller than 6 cm in diameter were 95% at 3 years and 85% at 5 years in group A, and 100% at 5 years in group B. We concluded that AAAs over 6 cm in diameter were an appropriate indication for surgery in octogenarians. | 18,958,558 |
Alpha-lipoic acid and ebselen prevent ischemia/reperfusion injury in the rat intestine. | Reactive oxygen species (ROS) and reactive nitrogen species (RNS), generated during tissue reperfusion, are characteristic of ischemia/reperfusion (I/R) injury. We conducted this study to evaluate the protective effect of alpha-lipoic acid (alpha-LA) and ebselen against intestinal I/R injury. Forty Sprague-Dawley rats were divided into five groups: a sham-operated group; an I/R group, subjected to intestinal ischemia for 45 min and reperfusion for 3 days; an I/R+alpha-LA group; an I/R+ebselen group; and an I/R+alpha-LA+ebselen group. We collected ileal specimens, to measure the tissue levels of malondialdehyde (MDA), protein carbonyl content (PCC), superoxide dismutase (SOD), and glutathione peroxidase (GPx), and to evaluate the histologic changes. There was a significant decrease in SOD and GPx levels, with an increase in MDA and PCC levels and intestinal mucosal injury in the intestinal I/R group (P<0.05). Superoxide dismutase and GPx levels were significantly higher, MDA and PCC levels were significantly lower, and intestinal injury was significantly less severe in the I/R+alpha-LA+ebselen group than in the I/R group (P<0.05). Although shortened villi and epithelial lifting were seen in the I/R group, only slight mucosal injury was seen in the treatment groups. alpha-Lipoic acid and ebselen played an important role in attenuating I/R injury of the intestine by scavenging ROS and RNS. | 18,958,562 |
Annular pancreas causing localized recurrent pancreatitis in a child: report of a case. | Annular pancreas is a rare congenital anomaly. We report a case of relapsing acute pancreatitis localized in the annulus of an annular pancreas in a young child. A 6-year-old boy complained of abdominal pain and we made a diagnosis of acute pancreatitis based on blood biochemistry results. Over the subsequent 12 months, he experienced two more pancreatitis-like attacks. Endoscopy revealed a duodenal stenosis in the second portion of the duodenum. Ultrasound, computed tomography, and magnetic resonance imaging depicted a ring of pancreatic tissue encircling the duodenum with a duct in the tissue, manifesting dilatation with a characteristic circular pattern around the duodenum. No dilatation of the dorsal pancreatic duct or pancreatic divisum was found. Based on these findings, we diagnosed acute pancreatitis localized in an annulus in an annular pancreas. This case report suggests that an annular pancreas may predispose to localized relapsing acute pancreatitis even in a child. | 18,958,567 |
Treatment of a citrin-deficient patient at the early stage of adult-onset type II citrullinaemia with arginine and sodium pyruvate. | Citrin deficiency is a common congenital metabolic defect not only in East Asian populations but also in other populations around the world. It has been shown that although liver transplantation is ultimately required in many patients to prevent neurological decompensation associated with hyperammonaemia, arginine is effective in lowering ammonia in hyperammonaemic patients, and a high-protein low-carbohydrate diet may provide some benefit to infants in improving failure to thrive. In the present study, the clinical symptoms and laboratory findings are reported for a 13-year-old citrin-deficient girl in the early stage of adult-onset type II citrullinaemia (CTLN2), and the therapeutic effect of orally administered arginine and sodium pyruvate was investigated. The patient complained of anorexia, lethargy, fatigue and poor growth, and showed laboratory findings typical of CTLN2; elevated levels of plasma citrulline, threonine-to-serine ratio, and serum pancreatic secretory trypsin inhibitor. Oral administration of arginine and sodium pyruvate for over 3 years improved her clinical symptoms and has almost completely normalized her laboratory findings. It is suggested that the administration of arginine and sodium pyruvate with low-carbohydrate meals may be an effective therapy in patients with citrin deficiency in order either to prolong metabolic normalcy or to provide a safer and more affordable alternative to liver transplantation. | 18,958,581 |
Comparative responsiveness and minimal change for the Oxford Elbow Score following surgery. | To assess the responsiveness and minimal change for the Oxford Elbow Score (OES) using anchor- and distribution-based approaches. A prospective observational study of 104 patients undergoing elbow surgery at a specialist orthopaedic hospital was carried out. Patients completed the OES and the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaires (both scored on a 0 to 100 scale) pre- and 6 months post-surgery. Transition items (used as anchors) assessed perceived changes following surgery. Indicators of responsiveness were the effect size; the anchor-based minimal clinically important difference (MCID) and best cut-point on the receiver operator characteristic (ROC) curve; and the distribution-based minimal detectable change (MDC). The three elbow-specific OES scales (Function, Pain, Social-Psychological) produced generally larger effect sizes (0.79, 1.14 and 1.18, respectively) than the upper-limb-specific DASH scale (0.76). Clear associations were observed between transition items and all OES and DASH scores (all r > |0.35|). The MCIDs for the OES Function scale and the DASH were similar (approximately 10), but were larger for the OES Pain and Social-Psychological scales (approximately 18), reflecting their lower (i.e. poorer) baseline scores and larger effect sizes. The MCIDs were, however, only consistently larger than the MDCs for the OES Pain domain. The OES Function scale and the DASH performed similarly on ROC analysis, but with the OES Pain and Social-Psychological scales demonstrating superior efficiency. For elbow surgery, the 12-item three-scale OES is highly responsive to 6-month post-operative outcomes, with its performance being generally better than that of the 30-item one-scale DASH. Study estimates of minimal change for the OES may be useful for informing sample size calculations and interpreting outcomes in future clinical trials. | 18,958,582 |
Haemato-biochemical responses and induction of HSP70 to dietary phosphorus in Catla catla (Hamilton) fingerlings. | A feeding trial of 120 days was conducted to study the effect of graded levels of dietary phosphorus on haematology, serum protein concentrations and HSP70 expression in fingerlings of the Indian major carp, Catla (Catla catla). Eight isonitrogenous and isoenergetic purified diets were formulated to contain graded levels of dietary phosphorus (dP), i.e., T(1), 0.1%; T(2), 0.3%; T(3), 0.5%; T(4), 0.7%; T(5), 0.9%; T(6), 1.1%; T(7), 1.3%; or T(8), 1.5%. Four hundred and eighty fish (average weight 4.23 +/- 0.016 g) were equally distributed into 24 tanks forming eight treatments with three replicates each. The fish were fed daily at the rate of 3.5% body weight in two instalments. At the end of feeding trial fish were sampled to study total RBC and WBC count, haemoglobin, serum lysozyme activity, serum total protein, albumin (A), globulin (G) concentration and HSP70 expression. Total RBC count, haemoglobin concentration and serum lysozyme activity did not vary significantly in response to different dietary phosphorus concentrations. Total WBC count was found to be significantly (P < 0.05) higher in T(1 )relative to all other treatments. Serum albumin and A/G ratio was found to be significantly lower in fish of T(1) and T(2) in relation to T(7) group (P < 0.05). Serum globulin and total protein levels remained unaffected by variations in dietary phosphorus. HSP70 expression was observed in T(1) group (0.1% dP) in gills and brain tissue, but not in liver and muscle tissues. No HSP70 expression was observed in fish of T(4) (0.7% dP) and T(8) (1.5% dP) treatments. These prima facie results suggest that dietary phosphorus had only minor influence on the haemato-biochemical parameters studied; however dietary phosphorus deficiency caused organ specific induction of HSP70 in catla fingerlings. | 18,958,586 |
Cypermethrin and lambda-cyhalothrin induced alterations in nucleic acids and protein contents in a freshwater fish, Channa punctatus. | In this study, a freshwater fish Channa punctatus was exposed to subacute concentrations of synthetic pyrethroid insecticides (cypermethrin and lambda-cyhalothrin) for 96 h to evaluate their impact on the levels of nucleic acids and protein in its different organs. Significant enhancement in the level of DNA was recorded in all tissues of the fish at high concentration of cypermethrin, whereas RNA and protein contents increased in tissues at all concentrations of cypermethrin tested. In contrast, lambda-cyhalothrin treatment caused an increase in the level of DNA only in liver and brain, whereas increase of RNA and protein varied to different levels in different tissues. Cypermethrin treatment induced RNA/DNA ratio in all fish organs tested, whereas lambda-cyhalothrin caused a sharp decrease in the ratio. Protein/DNA ratios were found to be tissue specific in treatments with both of the insecticides. The results clearly indicated that both of these pyrethroids exerted their effects in a similar manner in fish liver but differed in other tissues. These insecticides acted as potential biomodulators in C. punctatus, though following different routes. The results may be an indicator of aquatic pollution affecting freshwater fauna and flora and thus signaling the need for strict regulation on the indiscriminate input of pyrethroids from agricultural sites. | 18,958,590 |
Functional and stoichiometric analysis of subunit e in bovine heart mitochondrial F(0)F(1)ATP synthase. | The role of the integral inner membrane subunit e in self-association of F(0)F(1)ATP synthase from bovine heart mitochondria was analyzed by in situ limited proteolysis, blue native PAGE/iterative SDS-PAGE, and LC-MS/MS. Selective degradation of subunit e, without disrupting membrane integrity or ATPase capacity, altered the oligomeric distribution of F(0)F(1)ATP synthase, by eliminating oligomers and reducing dimers in favor of monomers. The stoichiometry of subunit e was determined by a quantitative MS-based proteomics approach, using synthetic isotope-labelled reference peptides IAQL*EEVK, VYGVGSL*ALYEK, and ELAEAQEDTIL*K to quantify the b, gamma and e subunits, respectively. Accuracy of the method was demonstrated by confirming the 1:1 stoichiometry of subunits gamma and b. Altogether, the results indicate that the integrity of a unique copy of subunit e is essential for self-association of mammalian F(0)F(1)ATP synthase. | 18,958,608 |
Poor response to pegylated interferon and ribavirin in older women infected with hepatitis C virus of genotype 1b in high viral loads. | Response to treatment in patients with chronic hepatitis C, with reference to age and gender, has not been examined fully. The influence of gender and age on treatment with pegylated interferon (PEG-IFN) and ribavirin was evaluated in a retrospective study. PEG-IFN and ribavirin were given for 48 weeks to 179 men and 121 women infected with hepatitis C virus (HCV) of genotype 1b in high viral loads (>100 kIU/ml). Sustained virological response at 24 weeks after treatment was poorer in women than men who were aged >or=50 years (22% vs 53%, P < 0.001). Among the patients aged >or=50 years who had received >or=80% of the doses of PEG-IFN, ribavirin, or both, women responded less often than men (26% vs 64%, P < 0.001; 33% vs 61%, P = 0.022; and 32% vs 63%, P = 0.016; respectively). In multivariate analysis, male gender, retention of indocyanine green, ribavirin dose and compliance with therapy increased sustained virological response. Response to combined PEG-IFN and ribavirin is poorer in female than male patients with hepatitis C who are aged >or=50 years, irrespective of compliance with treatment. Low estrogen levels in older women could be responsible for their impaired response to PEG-IFN and ribavirin. | 18,958,621 |
Characterization of Phaseolus vulgaris L. landraces cultivated in central Italy. | Eight Phaseolus vulgaris L. landraces cultivated on farm in marginal areas of Central Italy (Lazio region) were investigated in order to evaluate chemical composition of storage proteins and secondary metabolites fractions. The total protein content showed some differences among landraces; the maximum value was next to 30 g for 100 g of dry weight. The seed storage proteins were screened by polyacrylamide gel electrophoresis (SDS/PAGE): seven landraces exhibited phaseolin patterns type S, one landrace showed a phaseolin pattern type T. A morphological analysis of cotyledon parenchyma performed by scanning electron microscopy (SEM) revealed differences in size of starch granules. Moreover the polyphenolic composition was investigated using HPLC-APCI; from the methanol extracts a flavonoid, kaempferol, and a coumarin, 5,7-dimethoxycoumarin, were identified. To our knowledge, this is the first time that 5,7-dimethoxycoumarin has been reported in P. vulgaris seeds. | 18,958,625 |
Subsets and Splits
No community queries yet
The top public SQL queries from the community will appear here once available.