title stringlengths 0 1.13k | abstract stringlengths 1 15.7k | PMID int64 22 36.5M |
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Influence of medium components and fermentation conditions on the production of bacteriocin(s) by Bacillus licheniformis AnBa9. | Recently, antibacterial peptides are gaining more attention as an alternative therapeutics and food and other products from spoilage and deterioration. Antibacterial peptide producing strains were isolated from sediments of slaughterhouse sewage wastes. One among them, identified as Bacillus licheniformis inhibited the growth of several gram positive bacteria. Response surface methodology with central composite rotary design was used for optimization of fermentation medium and conditions for antibacterial peptide production. Lactose, NH(4)NO(3), yeast extract and NaCl and environmental factors such as pH, temperature and incubation period were selected as variables. Among ingredients, high concentration of yeast extract and NaCl had a positive effect on antibacterial peptide production and specific activity, respectively. Alkaline pH and high temperature favoured the production of antibacterial peptide by B. licheniformis AnBa9. Under optimized condition, B. licheniformis AnBa9 produced 25-fold higher production of antibacterial peptide than the un-optimized condition. Biochemical characteristics of the antibacterial peptides of B. licheniformis AnBa9 revealed that they are of bacteriocin type. | 18,762,415 |
Use of dewatered alum sludge as main substrate in treatment reed bed receiving agricultural wastewater: long-term trial. | This study aims to explore a novel application of dewatered alum sludge cakes (DASC) as the main medium in a single model reed bed to treat phosphorus-rich animal farm wastewater under "tidal flow" operation on a long-term basis. It is expected that the cakes act as the carrier for developing biofilm and also serve as adsorbent to enhance phosphorus (P) immobilization. Results have demonstrated that average removal efficiencies of 73.3+/-15.9% for COD, 82.9+/-12.3% for BOD(5), 86.4+/-6.0% for RP (reactive P), 88.6+/-7.2% for soluble reactive P (SRP) and 77.6+/-17.5% for SS can be achieved during the two year's operation. More significantly, the "P-adsorption proportion" by DASC in the reed bed is 42% of the overall P removal. The remaining removal of P may be contributed by the trapping and filtration process of DASC. Therefore, the lifetime of the DASC in reed bed is reasonably longer than that determined from the batch isotherm test. | 18,762,417 |
Design, synthesis, and antibacterial activities of novel 3,6-bicyclolide oximes: length optimization and zero carbon linker oximes. | We designed and synthesized a series of novel 3,6-bicyclolide oximes, possessing linkers of varying lengths to the secondary binding site. The E isomers exhibited excellent antibacterial profiles against a broad spectrum of resistant pathogens. | 18,762,418 |
Patterns of diversification in the discus fishes (Symphysodon spp. Cichlidae) of the Amazon basin. | We carried out a phylogeograhic and population genetic analysis of fishes of the taxonomically contentious genus Symphysodon from the Amazon basin in order to test hypotheses of relationships among taxonomic units, and potential processes driving diversification within this genus. We sampled 334 individuals of the genus Symphysodon from 24 localities that span the complete geographic distribution of this genus. The sampling scheme included all known phenotypic groups, species and subspecies. Analyses were based on 474 bp of the mitochondrial control region and 1443 bp of the exon 3 of RAG1 gene. We observed 102 mtDNA haplotypes defined by 89 segregating sites, and 5 nuDNA alleles defined by three segregating sites. Maximum-likelihood, Bayesian-inference and statistical parsimony analyses revealed three well defined monophyletic groups. These clades corresponded to the 'green' and 'blue' groups of Symphysodon aequifasciatus, and to a previously morphologically unrecognized clade from the Xingu River drainage. These three clades were nested within a paraphyletic assemblage consisting of the 'brown' group of S. aequifasciatus and of both described subspecies of S. discus, the 'Heckel' and the 'abacaxi' discus. Nuclear allele sharing was observed among groups, but there were significant differences in frequencies. We inferred several processes including past fragmentation among groups, and restricted gene flow with isolation by distance within the paraphyletic 'brown+Heckel+abacaxi' groups, and suggest that differences among the 'blue', 'Heckel' and 'brown' groups are potentially maintained by differences in water chemistry preferences. We further inferred colonization of the western Amazon basin by an ancestor of the 'green' clade. The 'green' group was the only group with a pattern of haplotype distribution consistent of a demographic expansion, and the divergence of this clade from other groups of discus was consistent with recent geologic evidence on the breach of the Purus Arch which separates western Amazon from eastern Amazon. We further hypothesized that the differentiation of the 'Xingu' clade could be due to vicariance events resulting from Pleistocene sea level, and thus Amazon River level fluctuations. We discuss the bearings of our results on the current taxonomy of this group, and on the biological reality of the different forms, subspecies and species of Symphysodon concluding that we are probably observing a process of diversification, and therefore taxonomy will remain contentious. | 18,762,435 |
Inconsistent use of terminology in whole body vibration exercise research. | Whole body vibration exercise (WBV) intensity can be manipulated by altering the frequency of oscillations and/or its magnitude. The inconsistencies and inaccuracies reported within the literature that at times challenge the replication and advancement of whole body vibration exercise research are discussed. Although frequency is regularly reported, inconsistency exists with the definition of vibration amplitude which has been interchangeably used with other terminology by some researchers. Of primary concern is the risk of injury to participants in future research. Researchers using intensities that were incorrectly reported by previous studies may unwittingly expose participants to harmful intensities. For clarity, an argument is put forward for the standardisation of terminology and reporting of whole body exercise parameters. | 18,762,453 |
Effect of a traditional Chinese medicine preparation Xindi soft capsule on rat model of acute blood stasis: a urinary metabonomics study based on liquid chromatography-mass spectrometry. | Xindi soft capsule is a traditional Chinese medicine preparation which consists of sea buckthorn flavonoids and sea buckthorn berry oil. In this study, a urinary metabonomics method based on the ultra-performance liquid chromatography combined with quadrupole time-of-flight tandem mass spectrometry (UPLC Q-TOF MS) was used to evaluate the efficacy and study the mechanism of traditional Chinese medicine preparation to blood stasis. With pattern recognition analysis (principal component analysis and partial least squares-discriminate analysis) of urinary metabolites, a clear separation of acute blood stasis model group and healthy control group was achieved, the dose groups were located between acute blood stasis model group and healthy control group showing a tendency of recovering to healthy control group, high dose and middle dose were more effective than low dose. Some significantly changed metabolites like cholic acid, phenylalanine and kynurenic acid have been found and identified and used to explain the mechanism. The work shows that the metabonomics method is a valuable tool in the research mechanism of traditional Chinese medicine. | 18,762,461 |
Muscarinic-3 acetylcholine receptor autoantibody in patients with systemic sclerosis: contribution to severe gastrointestinal tract dysmotility. | Patients with systemic sclerosis (SSc) complicated by severe gastrointestinal tract (GIT) dysmotility at an early stage are difficult to treat and mortality is high. To clarify the pathogenesis of GIT involvement, the occurrence of autoantibody was investigated for muscarinic-3 acetylcholine receptor (M3R) in patients with SSc. Fourteen patients with severe GIT involvement (malabsorption syndrome and/or pseudo-obstruction) within 2 years of SSc onset (group 1) were enrolled in the present study. Sixty-two patients with SSc without severe GIT involvement within 2 years of onset (group 2) were also recruited, along with 70 healthy control subjects. Using an established enzyme immunoassay (EIA) system detecting autoantibody against the second loop domain of M3R, the presence of an anti-M3R antibody was examined in SSc patients. The mean optical density (OD) titres of group 1 were significantly higher than those of group 2 (0.65 (SD 0.58) vs 0.066 (SD 0.13), p<0.001). The positivity of anti-M3R antibody was significantly higher in group 1 than in group 2 (9/14 vs 3/62, p = 2.5 x 10(-6) by Fisher's exact test). The cutoff OD was calculated from the EIA reaction of the 70 healthy controls (the mean value plus 2 SD was 0.295). The findings indicated that anti-M3R antibody very frequently appears in patients with SSc, which is accompanied by severe GIT involvement, suggesting that M3R-mediated enteric cholinergic neurotransmission may provide a pathogenic mechanism for GIT dysmotility in SSc. | 18,762,475 |
Bosque: integrated phylogenetic analysis software. | Phylogenetic analyses today involve dealing with computer files in different formats and often several computer programs. Although some widely used applications have integrated important functionalities for such analyses, they still work with local resources only: input/output files (users have to manage them) and local computing (users have sometimes to leave their programs, on their desktop computers, running for extended periods of time). To address these problems we have developed 'Bosque', a multi-platform client-server software that performs standard phylogenetic tasks either locally or remotely on servers, and integrates the results on a local relational database. Bosque performs sequence alignments and graphical visualization and editing of trees, thus providing a powerful environment that integrates all the steps of phylogenetic analyses. http://bosque.udec.cl | 18,762,483 |
Characteristics that distinguish abusive from nonabusive head trauma among young children who underwent head computed tomography in Japan. | Distinguishing abusive head trauma in young children from other diseases by symptoms is difficult in practice. Comparisons between abusive and nonabusive head trauma in young children in Japan, where computed tomography is widely and easily available, might contribute to identifying markers of abusive head trauma that differ from that in Western countries. The objective of this study was to compare the characteristics of abusive and nonabusive head trauma in young children in Japan. A comparative case series study involving a retrospective medical chart and social work record review of children who were aged 0 to 2 years, visited the National Center for Child Health and Development (Tokyo, Japan) from March 1, 2002, to December 31, 2005, and underwent computed tomography scanning because of suspected intracranial injury was performed. Patients (N = 260) were identified and classified as having either abusive or nonabusive head trauma on the basis of the published definition. Demographic and perinatal characteristics, injury history, clinical presentation, and outcomes were compared by using chi2 and Fisher's exact tests. Patients with abusive head trauma were significantly younger than patients with nonabusive head trauma and had a peak at approximately 2 to 4 and 7 to 9 months. Patients with abusive head trauma more likely presented no injury history by the caregiver, neurologic symptoms (unconsciousness, seizure, paralysis), subdural hemorrhage, and retinal hemorrhages. Although patients with abusive head trauma had severe clinical outcomes, only 32% of them were separated from the caregiver by social welfare services. This study highlights the several clinical markers to detect abusive head trauma at a medical visit, including an absence of injury history, neurologic symptoms, subdural hemorrhage, and retinal hemorrhage. These markers can be used to detect abusive head trauma cases by physicians and social welfare workers to protect children from additional abuse. | 18,762,487 |
Food security, maternal stressors, and overweight among low-income US children: results from the National Health and Nutrition Examination Survey (1999-2002). | A high proportion of children in the United States are overweight, suffer from food insecurity, and live in households facing maternal stressors. The objective of this article was to identify the associations of food insecurity and maternal stressors with childhood overweight among low-income children. We hypothesized that maternal stressors may exacerbate the relationship between food insecurity and child obesity. The sample included 841 children (3-17 years old) and their mothers with incomes below 200% of the poverty line from the 1999-2002 National Health and Nutrition Examination Survey. Food insecurity was based on US Department of Agriculture protocol, maternal stressors were assessed from survey questions, and BMI was used to classify weight status. Probit regression models predicted the probability of a child being overweight or obese. In most specifications, there was no direct association between food insecurity or maternal stressors and overweight for children of any age. Among 3- to 10-year-olds, the interaction of food insecurity and maternal stressors was significantly linked to the probability of being overweight; more specifically, an increase in maternal stressors amplified a food secure child's probability of being overweight or obese. This result is robust to alternative specifications. However, these results were not found among 11- and 17-year-old youth. Younger children in food secure, low-income households in the United States who are experiencing higher levels of maternal stressors have a greater probability of being overweight than food insecure children. This finding was contrary to the hypothesis; 3 reasons for this are covered in the article. Those who create policies that address childhood obesity could consider the benefits to low-income children's well-being resulting from reducing their mothers' stressors. Because most children in the United States are food secure, these policies could have a profound impact on childhood overweight. | 18,762,488 |
Safety monitoring of drugs receiving pediatric marketing exclusivity. | The Food and Drug Administration Modernization Act provided for an additional 6-month period of marketing exclusivity to companies that perform pediatric drug trials in response to a Food and Drug Administration-issued written request. Because many safety concerns cannot be detected until after the introduction of a product to a larger and more diverse market, the Best Pharmaceuticals for Children Act required the Food and Drug Administration to report to the Pediatric Advisory Committee on adverse events occurring during the 1-year period after granting pediatric exclusivity. We sought to describe the Pediatric Advisory Committee's recommendations made in response to safety reviews informed by data from the Food and Drug Administration Adverse Event Reporting System in 67 drugs granted exclusivity. Pediatric Advisory Committee meetings and data presented by the Food and Drug Administration for all drugs were reviewed from June 2003 through April 2007. We divided the drugs into 2 groups: those that were returned to routine adverse event monitoring and those that had specific Pediatric Advisory Committee recommendations. Forty-four (65.7%) drugs were returned to routine monitoring for adverse events. The Pediatric Advisory Committee, sometimes working with other advisory committees, recommended label changes for 12 (17.9%) drugs, continued monitoring for 10 (14.9%), production of MedGuides for 9 (13.4%), and an update on label changes resulting from discussions with the sponsor for 1 (1.5%) drug. Some drugs had >1 action. Several of the adverse events revealed during this process were rare and life-threatening. Safety monitoring during the early postmarketing period is crucial to detect rare, serious, or pediatric-specific adverse events. Fortunately, the majority of drugs given exclusivity had no adverse events of a frequency or severity that prevented a return to routine adverse event monitoring. | 18,762,496 |
First successful bone marrow transplantation for X-linked chronic granulomatous disease by using preimplantation female gender typing and HLA matching. | Allogeneic hematopoietic stem cell transplantation from an human leukocyte antigen (HLA)-identical donor is currently the only proven curative treatment for chronic granulomatous disease. Hematopoietic stem cell transplantation with alternative donors is associated with higher morbidity and mortality. Therefore, we performed in vitro fertilization and preimplantation HLA matching combined with female sexing for hematopoietic stem cell transplantation in chronic granulomatous disease. Ethical and psychological issues were considered carefully. We used in vitro fertilization with X-enriched spermatozoa followed by preimplantation genetic diagnosis to identify female HLA-genoidentical embryos in a family in need of a suitable donor for their boy affected with severe X-linked chronic granulomatous disease. Two preimplantation genetic diagnosis cycles were performed in the family. In the second cycle, 2 HLA-genoidentical female embryos were transferred and a singleton pregnancy was obtained, resulting in the birth of an unaffected girl at term. Because of insufficient cell numbers in the cord-blood source, conventional hematopoietic stem cell transplantation had to be performed at 12 months of age of the donor and 5 years of age of the recipient and resulted in complete stable donor chimerism and immunologic reconstitution up to 25 months post-hematopoietic stem cell transplantation. Hematopoietic stem cell transplantation after in vitro fertilization and combined female sexing and HLA matching offers a new and relatively rapid therapeutic option for patients with X-linked primary immunodeficiency such as chronic granulomatous disease who need hematopoietic stem cell transplantation but lack an HLA-genoidentical donor. | 18,762,514 |
Early language outcomes of early-identified infants with permanent hearing loss at 12 to 16 months of age. | The objectives of this study were to determine the early language outcomes of children with mild to profound hearing loss, compared with hearing control children, at 12 to 16 months of age and to examine the effects of "very early" enrollment (</=3 months) in early intervention. This was a prospective longitudinal study of the outcomes of a cohort of 30 infants identified in the Rhode Island universal newborn hearing screening program and 96 hearing control subjects. Eligible families with children with all degrees of congenital hearing loss were invited to enroll. Child language skills were assessed by using the MacArthur-Bates Communicative Development Inventory, Words and Gestures, at 12 to 16 months. Children with moderate/profound hearing loss had significantly lower numbers of phrases understood, words understood, and early, later, and total gestures, compared with children with mild/minimal hearing loss and hearing control subjects. Furthermore, children with hearing loss who were enrolled in early intervention at </=3 months had significantly higher percentile scores for number of words understood, words produced, and early, later, and total gestures, compared with those enrolled at >3 months. Regression analyses to test the independent effects on language skills of children with hearing loss identified enrollment in early intervention at </=3 months as an independent predictor of percentile scores for word and early gesture production. Very early enrollment (</=3 months) in early intervention has beneficial effects on early language for children with hearing loss. Nevertheless, 12- to 16-month-old children with moderate/profound hearing loss exhibit delayed receptive and expressive language skills in oral and signed English modes, compared with peers with either mild/minimal hearing loss or typical hearing sensitivity. | 18,762,523 |
Values parents apply to decision-making regarding delivery room resuscitation for high-risk newborns. | The aim of this study was to characterize parental decision-making regarding delivery room resuscitation for infants born extremely prematurely or with potentially lethal congenital anomalies. This was a qualitative multicenter study. We identified English-speaking parents at 3 hospitals whose infants had died as a result of extreme prematurity or lethal congenital anomalies in 1999-2005. Parents were interviewed about their prenatal decision-making. Maternal medical charts were reviewed for documented discussions regarding delivery room resuscitation. Subject enrollment was stopped when saturation of themes was achieved. Twenty-six mothers of infants were interviewed. All parents wanted to participate to some degree in decisions regarding delivery room resuscitation. Few parents recalled discussing options for delivery room resuscitation with physicians, and even fewer recalled being offered the option of comfort care, even when these discussions were documented in the medical chart. Parents did not report physicians' predictions of morbidity and death to be central to their decision-making. Religion, spirituality, and hope guided decision-making for most parents. Some parents felt that they had not made any decisions regarding resuscitation and instead "left things in God's hands." These parents typically were documented by staff members to "want everything done." The values that parents find most important during decision-making regarding delivery room resuscitation may not be addressed routinely in prenatal counseling. Parents and physicians may have different interpretations of what is discussed and what decisions are made. Future work should investigate whether physicians can be trained to address effectively parents' values during the decision-making process and whether addressing these values may improve physician-parent communication and lead to better postdecision outcomes for parents. | 18,762,529 |
Blood leucocyte telomere DNA content predicts vascular telomere DNA content in humans with and without vascular disease. | Previous studies have suggested that reduced telomere length in circulating leucocytes in humans is associated with premature vascular disease and by implication, accelerated vascular ageing. Importantly, a link between telomere length in circulating leucocytes and the blood vessel wall has never been established. We, thus, investigated the relationship between vascular wall and circulating leucocyte telomere length in humans with and without overt vascular disease. Aortic biopsies and paired blood leucocytes were obtained from 20 patients with asymptomatic abdominal aortic aneurysms (AAAs), undergoing elective open repair, and 12 morphologically normal aortas from a group of cadaveric organ donors of similar mean age. Telomere content was compared by quantitative PCR and expressed as telomere:genomic DNA ratio. The telomere:genomic DNA content was significantly reduced in wall biopsies of AAA vs. normal aorta, and this difference remained after adjusting for age and gender. There were strong correlations between leucocyte and vascular telomere content when the AAA and control groups were analysed either separately or grouped irrespective of the presence of vascular disease (r = 0.62, P < 0.001). The findings demonstrate that leucocyte DNA content is predictive of vascular telomere content and is an accurate surrogate for human vascular age. | 18,762,552 |
Biochemical markers of myocardial remodelling in hypertensive heart disease. | The intricate mechanisms responsible for the structural remodelling of the myocardium that facilitates the evolution to heart failure in hypertensive patients, namely in those with left ventricular hypertrophy, requires from clinicians the utilization of a multibiomarker approach for short-term and long-term stratification as well as prognostication of patients. Biochemical markers may also help to identify patients with no clinical evidence of hypertensive heart disease, and provide information about the need for more aggressive therapy during different stages of the disease, and potentially provide valuable biochemical data for the specialist. Although there is a continuous and complex interplay between biochemical and imaging markers, perhaps their use will also have the potential to modify the medical management of patients with hypertensive heart disease and therapeutic decision-making by tailoring a targeted therapy according to the predominant mechanism of myocardial remodelling. This article will review in brief the most relevant information on a panel of circulating molecules that may accomplish the criteria required to be considered as biochemical markers of the cardiomyocyte and non-cardiomyocyte structural changes that occur in the hypertensive myocardium. | 18,762,556 |
Inhibition of specific HDACs and sirtuins suppresses pathogenesis in a Drosophila model of Huntington's disease. | Huntington's disease (HD) is associated with transcriptional dysregulation, and multiple studies with histone deacetylase (HDAC) inhibitors suggest that global approaches for restoring transcriptional balance and appropriate protein acetylation are therapeutically promising. To determine whether more targeted approaches might be effective, we have tested the impact of all the HDACs in Drosophila on Huntingtin (Htt)-induced pathology. Among the zinc-dependent or 'classic' HDACs, we find that neurodegeneration is most sensitive to levels of Rpd3. We also find that among the NAD(+)-dependent class III deacetylases, genetic or pharmacological reduction of either Sir2 or Sirt2 provides neuroprotection to Htt-challenged animals and that even greater neuroprotection is achieved when Rpd3 and Sir2 are simultaneously reduced. Our experiments suggest that longevity promoting strategies may be distinct from those that protect against neurodegeneration in Drosophila challenged with mutant human Htt. These results highlight a novel therapeutic approach for HD in the form of Sir2 inhibition and possible combinatorial inhibition of Sir2 and Rpd3. | 18,762,557 |
Use of recombinant human interferon alpha-2a in the management of a dog with epitheliotropic lymphoma. | An 8-year-old, mixed-breed dog with preputial epitheliotropic lymphoma was initially treated with cyclophosphamide, vincristine, and prednisolone. A short-term partial response was followed by disease progression after 4 weeks. Recombinant human interferon alpha-2a was administered starting at week 7. The interferon therapy resulted in rapid resolution of clinical signs and a 10-week disease-free interval. The lymphoma recurred at 17 weeks and did not respond to rescue chemotherapy. Additional oral lesions were treated with localized radiotherapy followed by increased dosages of interferon. This additional interferon treatment resulted in another 12 weeks of stable disease. | 18,762,565 |
Recruitment of PCM1 to the centrosome by the cooperative action of DISC1 and BBS4: a candidate for psychiatric illnesses. | A role for the centrosome has been suggested in the pathology of major mental illnesses, especially schizophrenia (SZ). To show that pericentriolar material 1 protein (PCM1) forms a complex at the centrosome with disrupted-in-schizophrenia 1 (DISC1) and Bardet-Biedl syndrome 4 protein (BBS4), which provides a crucial pathway for cortical development associated with the pathology of SZ. To identify mutations in the PCM1 gene in an SZ population. Interaction of DISC1, PCM1, and BBS proteins was assessed by immunofluorescent staining and coimmunoprecipitation. Effects of PCM1, DISC1, and BBS on centrosomal functions and corticogenesis in vivo were tested by RNA interference. The PCM1 gene was examined by sequencing 39 exons and flanking splice sites. Probands and controls were from the collection of one of us (A.E.P.). Thirty-two probands with SZ from families that had excess allele sharing among affected individuals at 8p22 and 219 white controls. Protein interaction and recruitment at the centrosome in cells; neuronal migration in the cerebral cortex; and variant discovery in PCM1 in patients with SZ. PCM1 forms a complex with DISC1 and BBS4 through discrete binding domains in each protein. DISC1 and BBS4 are required for targeting PCM1 and other cargo proteins, such as ninein, to the centrosome in a synergistic manner. In the developing cerebral cortex, suppression of PCM1 leads to neuronal migration defects, which are phenocopied by the suppression of either DISC1 or BBS4 and are exacerbated by the concomitant suppression of both. Furthermore, a nonsense mutation that segregates with SZ spectrum psychosis was found in 1 family. Our data further support for the role of centrosomal proteins in cortical development and suggest that perturbation of centrosomal function contributes to the development of mental diseases, including SZ. | 18,762,586 |
Genomewide association analysis followed by a replication study implicates a novel candidate gene for neuroticism. | Neuroticism is a trait that reflects a tendency toward negative mood states. It has long been linked to internalizing psychiatric conditions, such as anxiety and depression, and it accounts for much of the substantial comorbidity seen between these disorders. To identify common genetic variants that affect neuroticism to better understand (the comorbidity between) a broad range of psychiatric disorders and to develop effective treatments. More than 420,000 genetic markers were tested for their association with neuroticism in a genomewide association study (GWAS). The GWAS sample consisted of 1227 healthy individuals ascertained from a US national sampling frame and available from the National Institute of Mental Health genetics repository. The most promising markers were subsequently tested in a German replication sample comprising 1880 healthy individuals. A strict definition of replication (same marker, same direction of effects, and same measure) combined with a threshold we proposed previously for declaring significance in genetic studies that ensures a mean probability of producing false-positive findings of less than 10%. The most promising results in the GWAS and replication samples were single-nucleotide polymorphisms (SNPs) in the gene MAMDC1. These SNPs all tagged the same 2 haplotypes and had P values of 10(-5) to 10(-6) in the GWAS sample and of .006 to .02 in the replication sample. Furthermore, the replication involved the same SNPs and the same direction of effects. In a combined analysis of all data, several SNPs were significant according to the threshold that allows for 10% false-positive findings. The small effect sizes may limit the prognostic, diagnostic, and therapeutic use of SNP markers such as those in MAMDC1. However, the present study demonstrates the potential of a GWAS to discover potentially important pathogenic pathways for which clinically more powerful (bio)markers may eventually be developed. | 18,762,592 |
Depressive symptoms in youth heads of household in Rwanda: correlates and implications for intervention. | To examine the level of depressive symptoms and their predictors in youth from one region of Rwanda who function as heads of household (ie, those responsible for caring for other children) and care for younger orphans. Cross-sectional survey Four adjoining districts in Gigonkoro, an impoverished rural province in southwestern Rwanda. Trained interviewers met with the eldest member of each household (n = 539) in which a youth 24 years old or younger was caring for 1 child or more. Serving as a youth head of household. Rates and severity of depressive symptoms using the Center for Epidemiologic Studies Depression scale; measures of grief, adult support, social marginalization, and sociodemographic factors using scales developed for this study. Of the 539 youth heads of household, 77% were subsistence farmers and only 7% had attended school for 6 years or more. Almost half (44%) reported eating only 1 meal a day in the last week, and 80% rated their health as fair or poor. The mean score on the Center for Epidemiologic Studies Depression scale was 24.4, exceeding the most conservative published cutoff score for adolescents. Multivariate analysis revealed that reports of depressive symptoms that exceeded the clinical cutoff were associated with having 3 basic household assets or fewer, such as a mattress and a spare set of clothes (odds ratio [OR], 1.69; 95% confidence interval [CI], 1.06-2.70), eating less than 1 meal per day (OR, 1.68; 95% CI, 1.09-2.60), reporting fair health (OR, 1.32; 95% CI, 0.76-2.29) or poor health (OR, 2.33; 95% CI, 1.17-4.64), endorsing high levels of grief (OR, 2.67; 95% CI, 1.73-4.13), having at least 1 parent die in the genocide as opposed to all other causes of parental death (OR, 1.83; 95% CI, 1.10-3.04), and not having a close friend (OR, 1.91; 95% CI, 1.17-3.12). There was an interaction between marginalization from the community and alcohol use; youth who were highly marginalized and did not drink alcohol were more than 3 times more likely to report symptoms of depression (OR, 3.07; 95% CI, 1.73-5.42). When models were constructed by grouping theoretically related variables into blocks and controlling for other blocks, the emotional status block of variables (grief and marginalization) accounted for the most variance in depressive symptoms. Orphaned youth who head households in rural Rwanda face many challenges and report high rates of depressive symptoms. Interventions designed to go beyond improving food security and increasing household assets may be needed to reduce social isolation of youth heads of household. The effect of head-of-household depressive symptoms on other children living in youth-headed households is unknown. | 18,762,600 |
Anaphylaxis following quadrivalent human papillomavirus vaccination. | In 2007, Australia implemented the National human papillomavirus (HPV) Vaccination Program, which provides quadrivalent HPV vaccine free to all women aged 12-26 years. Following notification of 7 presumptive cases of anaphylaxis in the state of New South Wales, Australia, we verified cases and compared the incidence of anaphylaxis following HPV vaccination to other vaccines in comparable settings. We contacted all patients with suspected anaphylaxis and obtained detailed histories from telephone interviews and a review of medical records. A multidisciplinary team determined whether each suspected case met the standardized Brighton definition. Some participants also received skin-prick allergy testing for common antigens and components of the HPV vaccine. Of 12 suspected cases, 8 were classified as anaphylaxis. Of these, 4 participants had negative skin-prick test results for intradermal Gardasil. From the 269 680 HPV vaccine doses administered in schools, 7 cases of anaphylaxis were identified, which represents an incidence rate of 2.6 per 100 000 doses (95% CI 1.0-5.3 per 100 000). In comparison, the rate of identified anaphylaxis was 0.1 per 100 000 doses (95% CI 0.003-0.7) for conjugated meningococcal C vaccination in a 2003 school-based program. Based on the number of confirmed cases, the estimated rate of anaphylaxis following quadrivalent HPV vaccine was significantly higher than identified in comparable school-based delivery of other vaccines. However, overall rates were very low and managed appropriately with no serious sequelae. | 18,762,618 |
Patient risk related to common dental radiographic examinations: the impact of 2007 International Commission on Radiological Protection recommendations regarding dose calculation. | In 2007, the International Commission on Radiological Protection (ICRP) revised estimates of the radiosensitivity of tissues including those in the maxillofacial region. The authors conducted a study to reassess patients' risk related to common dental radiographic exposures using the 2007 ICRP recommendations. The authors used a tissue-equivalent head phantom to measure dose. They calculated effective doses by using both 1990 and revised 2007 ICRP recommendations. Effective dose is a calculation that takes into consideration the different sensitivities of organs to long-term effects from ionizing radiation. It is the preferred method for comparing doses between different types of exposures. Effective doses (per the 2007 ICRP) in microsieverts were as follows: full-mouth radiographs (FMX) with photo-stimulable phosphor (PSP) storage or F-speed film with rectangular collimation, 34.9 microSv; four-image posterior bitewings with PSP or F-speed film with rectangular collimation, 5.0 microSv; FMX using PSP or F-speed film with round collimation, 170.7 microSv; FMX with D-speed film and round collimation, 388 microSv; panoramic Orthophos XG (Sirona Group, Bensheim, Germany) with charge-coupled device (CCD), 14.2 microSv; panoramic ProMax (Planmeca, Helsinki, Finland) with CCD, 24.3 microSv; posteroanterior cephalogram with PSP, 5.1 microSv; and lateral cephalogram with PSP, 5.6 microSv. These values are 32 to 422 percent higher than those determined according to the 1990 ICRP guidelines. Although radiographs are an indispensable diagnostic tool, the increased effective doses of common intraoral and extraoral imaging techniques are high enough to warrant reconsideration of means to reduce patients' exposure. Clinicians can reduce patients' dose substantively by using digital receptors or F-speed film instead of D-speed film, rectangular collimation instead of round collimation and radiographic selection criteria. | 18,762,634 |
Dentists in double trouble: the (un)fairness of punishing for the same mistake twice. | and Overview. Many state dental practice acts allow for the suspension or revocation of a dentist's license on the basis of a previous conviction for illegal behavior, even if the behavior is not related to the practice of dentistry. Penalizing a dentist twice for the same behavior appears to violate the legal principle "ne bis in idem"-that is, no double penalty for the same socially undesirable behavior. However, disciplinary measures are not intended primarily to penalize the offender but rather to protect the public and the reputation of the profession. In this article, the authors review various cases in which boards disciplined convicted dentists and propose criteria for discerning between situations in which such "double trouble" is fair and unfair. and Practice Implications. The authors conclude that such disciplinary actions are fair only if four criteria concerning the following are fulfilled: the relationship between the dentist's illegal behavior and dental treatment or privileges of the dentist; the severity of the crime; the frequency of the illegal behavior; and the balance between crime and punishment. | 18,762,636 |
Total hip replacement in patients eighty years of age and older. | The number of people eighty years of age and older in developed countries is increasing, with a concomitant increased demand for total hip replacement. We analyzed the outcomes of total hip arthroplasty for patients in this age group using data from the Finnish National Arthroplasty Registry. Data from the Finnish Arthroplasty Registry on 6540 patients (6989 hips) who were eighty years of age or older at the time of a total hip arthroplasty, performed between 1980 and 2004, were evaluated with use of survival analyses. Factors affecting survivorship rates were sought, and the reasons for revision were identified. The mean age of the patients undergoing a primary total hip arthroplasty was 82.7 years. The mean longevity of 3065 patients who died following total hip arthroplasty was 5.1 years. With revision total hip arthroplasty for any reason as the end point, Kaplan Meier survivorship was 97% (95% confidence interval, 96% to 97%) at five years (2617 hips) and 94% (95% confidence interval, 93% to 95%) at ten years (532 hips). Of the 195 hip replacements that required revision, 183 had information on the reason for revision. Eighty-four (46%) were revised for aseptic loosening; thirty-six (20%), for recurrent dislocation; twenty-four (13%), for a periprosthetic fracture; and twenty-three (13%), for infection. Seven hundred and twenty-nine patients had undergone hybrid fixation (a cemented stem and a cementless cup). The survivorship of these replacements was significantly better than that for replacements with cementless fixation in 399 patients (p < 0.05). In patients who had a total hip arthroplasty when they were more than eighty years old, the prevalence of aseptic loosening was less than that encountered in younger patients, but recurrent dislocation, periprosthetic fracture, and infection were more common in this age group. Cementation of the femoral stem demonstrated better long-term results than cementless fixation, indicating that it may provide better initial fixation and, therefore, longer life-in-service. | 18,762,648 |
Interlocking contoured intramedullary nail fixation for selected diaphyseal fractures of the forearm in adults. | Plate osteosynthesis is the most commonly used technique for the treatment of diaphyseal forearm fractures in adults. However, application of a plate can disrupt the periosteal blood supply and necessitates skin incisions that may be unsightly, and there is a risk of refracture if the implant is removed. The purpose of this study was to assess the early results of the use of a contoured interlocking intramedullary nail to stabilize displaced diaphyseal fractures of the forearm. Between January 2004 and July 2006, a total of thirty-eight interlocking intramedullary nails were inserted into the forearms of twenty-seven adults. Eighteen nails were used in the radius and twenty were used in the ulna to stabilize a diaphyseal fracture. The mean follow-up period was seventeen months. Functional outcomes were assessed with use of the Grace and Eversmann rating system, and patient-rated outcomes were assessed by completion of the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire. The average time to fracture union was fourteen weeks. There was one nonunion of an open comminuted fracture of the middle third of the ulna. There were no deep infections or radioulnar synostoses. According to the Grace and Eversmann rating system, twenty-two patients (81%) had an excellent result; three (11%), a good result; and two (7%), an acceptable result. The DASH scores averaged 15 points (range, 5 to 61 points). Our experience indicates that the advantages of an interlocking intramedullary nail system for the radius and ulna are that it is technically straightforward, it allows a high rate of osseous consolidation, and it requires less surgical exposure and operative time than does plate osteosynthesis. We suggest that the interlocking intramedullary nail system be considered as an alternative to plate osteosynthesis for selected diaphyseal fractures of the forearm in adults. | 18,762,649 |
Traumatic anterosuperior rotator cuff tears: the outcome of open surgical repair. | Anterosuperior rotator cuff tears involving the subscapularis and supraspinatus tendons are less common than posterosuperior tears and are rarely discussed in the literature. The purpose of this study was to identify the unique features of this injury and to assess the outcome of operative treatment. Thirty consecutive patients, with a mean age of fifty-seven years (range, forty-three to seventy-three years), had an open repair of a traumatic anterosuperior rotator cuff tear. Twenty-four patients (80%) were male. Sixteen patients (53%) had involvement of the dominant shoulder, twenty-three (77%) had a biceps tendon disorder, and sixteen (53%) had a positive lift-off maneuver prior to surgery. Surgical approaches included an isolated superior deltoid-splitting approach in twenty patients, an isolated deltopectoral approach in five patients, and a combined approach in five patients. Open repair was performed at a mean of 4.5 months after the injury or the onset of symptoms. The final outcomes were determined with a physical examination and patient self-assessed outcome tools. At a mean follow-up of fifty-six months, twenty-one of the thirty patients were satisfied with their symptoms, and twenty-nine would have the surgery again. The mean pain score on the visual analog scale improved from 6.2 to 1.2 (p < 0.001). The mean score on the Disabilities of the Arm, Shoulder and Hand questionnaire improved from 41.7 to 12.2 (p < 0.001). The mean percentage of functions that patients were able to perform on the Simple Shoulder Test improved from 36.4% to 82.8% (p < 0.001). The mean age and sex-adjusted Constant score was 93.4 postoperatively. The mean elevation, external rotation, and internal rotation of the involved shoulders were 97%, 109%, and 97%, respectively, of those of the contralateral side. The mean strength of elevation, external rotation, and internal rotation were 85%, 93%, and 101%, respectively, of those of the contralateral side. Infraspinatus involvement (p = 0.04), the extent of the supraspinatus tear (p = 0.03), and a Workers' Compensation claim (p = 0.03) were associated with worse outcomes and decreased satisfaction. Patients with a traumatic anterosuperior rotator cuff tear present with internal rotation weakness, and they usually have a biceps tendon disorder. While larger tears involving greater portions of the supraspinatus and extending into the infraspinatus are associated with poorer outcomes, early recognition of this injury and open repair can reliably restore shoulder function to near normal levels. | 18,762,651 |
Computerized tomographic morphometric analysis of subaxial cervical spine pedicles in young asymptomatic volunteers. | Although cervical spine pedicle screws have been shown to provide excellent fixation, widespread acceptance of their use is limited because of the risk of injury to the spinal cord, nerve roots, and vertebral arteries. The risks of pedicle screw insertion in the cervical spine can be mitigated by a three-dimensional appreciation of pedicle anatomy. Normative data on three-dimensional subaxial pedicle geometry from a large, young, and asymptomatic North American population are lacking. The purpose of the present study was to determine three-dimensional subaxial pedicle geometry in a large group of young volunteers and to determine level and sex-specific morphologic differences. Helical computerized tomography scans were made from the third cervical to the seventh cervical vertebra in ninety-eight volunteers (sixty-three men and thirty-five women) with an average age of twenty-five years. Pedicle width, height, length, and transverse and sagittal angulations were measured bilaterally. Pedicle screw insertion positions were quantified in terms of mediolateral and superoinferior offsets relative to readily identifiable landmarks. The mean pedicle width and height at all subaxial levels were sufficient to accommodate 3.5-mm screws in 98% of the volunteers. Pedicle width and height dimensions of <4.0 mm were rare (observed in association with only 1.7% of the pedicles), with 82% occurring in women and 72% occurring unilaterally. Screw insertion positions generally moved medially and superiorly at caudal levels. Transverse angulation was approximately 45 degrees at the third to fifth cervical levels and was less at more caudal levels. Sagittal angulation changed from a cranial orientation at superior levels to a caudal orientation at inferior levels. Mediolateral and superoinferior insertion positions and sagittal angulations were significantly dependent (p < 0.05) on sex and spinal level. Transverse angulation was significantly dependent (p < 0.05) on spinal level. Pedicle screw insertion points and orientation are significantly different (p < 0.05) at most subaxial cervical levels and between men and women. Preoperative imaging studies should be carefully templated for pedicle size in all patients on a level-specific basis. Although the prevalence was low, women were more likely to have pedicle width and height dimensions of <4.0 mm. | 18,762,652 |
Linked elbow replacement: a salvage procedure for distal humeral nonunion. | Nonunion is a challenging and not uncommon complication of distal humeral fractures. Our long-term experience with linked semiconstrained total elbow arthroplasty as a salvage procedure for patients with distal humeral nonunion not amenable to internal fixation was investigated. Ninety-one consecutive patients (ninety-two elbows) underwent total elbow arthroplasty for the treatment of a distal humeral nonunion, and the results were reviewed at a mean of 6.5 years postoperatively. Patients' charts and anteroposterior and lateral radiographs made prior to and immediately after the joint replacement and at the time of the latest follow-up were reviewed to identify intraoperative and postoperative complications, and radiographic evidence of loosening or bushing wear. The outcome measures consisted of prosthetic survival, with implant removal as the end point for failure, and the Mayo Elbow Performance Score (MEPS). At the time of the most recent follow-up, joint stability had been initially restored in all patients, including nine who had had a grossly flailed elbow. Sixty-seven (74%) of the patients had no pain or mild pain at the time of the latest follow-up, whereas seventy-nine patients (87%) had had moderate or severe pain prior to the surgery. While 85% (seventy-seven) of the ninety-one patients rated the outcome as better or much better, twenty patients (22%) had a fair or poor MEPS. A total of forty-four complications occurred in forty elbows, and there were thirty-two reoperations, twenty-three of which involved implant revision or removal. Factors that increased the risk of implant failure were a patient age of less than sixty-five years, two or more prior surgical procedures, and a history of infection. The rate of prosthetic survival without removal or revision for any reason was 96% at two years, 82% at five years, and 65% at both ten and fifteen years. Linked semiconstrained total elbow arthroplasty is a salvage procedure that can provide pain relief and restore motion and function in patients with a distal humeral nonunion that is not amenable to internal fixation. Substantial risk factors for failure include an age of less than sixty-five years, multiple previous surgical procedures, and any history of infection. | 18,762,655 |
Arthroscopic surgery for primary traumatic patellar dislocation: a prospective, nonrandomized study comparing patients treated with and without acute arthroscopic stabilization with a median 7-year follow-up. | No data exist whether patients with primary traumatic patellar dislocation benefit from initial arthroscopic medial repair surgery. To compare long-term outcomes of patients treated with acute arthroscopic stabilization for patellar dislocation with those treated nonoperatively except for removal of loose bodies. Cohort study; Level of evidence, 2. The study group included 76 consecutive military recruits (72 men, 4 women), with a median age of 20 years (range, 19-22) at the time of dislocation. Thirty patients (group 1) underwent initial arthroscopic medial retinacular repair, and 46 patients (group 2) were treated without stabilizing surgery, including 11 who had osteochondral fragments arthroscopically removed. Patients with previous patellar dislocations or instability were excluded. Aftercare was identical in both groups. Redislocations, subjective symptoms, and functional limitations were evaluated after a median 7-year follow-up. Sixty-one (80%) patients participated in a follow-up examination. At final follow-up, 8 (23%) redislocations occurred in group 2 and 5 (19%) in group 1 (P = .84). Eight (23%) patients in group 2 and 3 (12%) in group 1 reported patellar subluxations (P = .18). In group 1, 81% regained their preinjury activity level compared with 56% in group 2 (P = .05). Functional outcomes were good in both groups (Kujala scores: 87 for group 1 and 90 for group 2) (P = .22). Regarding the presence of osteoarthritic characteristics in the patellofemoral joint, no statistically significant differences were found between the groups. Initial arthroscopic medial retinacular repair was not followed by improved patellar stability nor reduced incidence of redislocations compared with nonoperative (except for removal of loose bodies) treatment. Acute arthroscopic medial retinacular repair allowed patients to better regain preinjury activity level than in patients not undergoing retinacular repair. The decision to stabilize the patella by initial arthroscopic surgery should be made with caution. | 18,762,668 |
Amplatzer device closure of a tortuous Gerbode (left ventricle-to-right atrium) defect complicated by transient hemolysis in an octogenarian. | An 86 year-old male presented with progressive shortness of breath and a murmur. Six years earlier, he had undergone mitral valve surgery. An echocardiogram revealed a significant left ventricular-to-right atrial connection (Gerbode defect). The defect was closed percutaneously using an Amplatzer Septal Occluder device. After the procedure, the patient developed transient hemolysis and renal dysfunction. A year later, there was no residual flow on echocardiography and the patient reported marked improvement in exercise tolerance. | 18,762,687 |
Large somatostatin-producing endocrine carcinoma of the ampulla of vater in association with GIST in a patient with von Recklinghausen's disease. Case report and review of the literature. | Somatostatin-producing endocrine tumors of the duodenum are very rare neoplasms of the gastrointestinal tract. These tumors may be associated with von Recklinghausen's disease. We present the case of a 49-year-old female patient with von Recklinghausen's disease and an incidentally diagnosed ampullary neoplasm. The patient was treated with a classical pancreaticoduodenectomy. At surgery, a mass was found in the greater curve of the stomach which was resected using the classic Whipple procedure. Histology and immunohistochemistry showed that the duodenal tumor was an ampullary somatostatin-producing endocrine carcinoma while the gastric tumor was a gastrointestinal stromal tumor (GIST). The postoperative course was uneventful and the patient is alive, without tumor recurrence, six years after surgery. Somatostatin-producing endocrine tumors of the duodenum are rare tumors, often associated with von Recklinghausen's disease; these neoplasms should be treated aggressively using radical surgical resection. Although local resection may be appropriate for small duodenal somatostatin-producing tumors, a pancreaticoduodenectomy is usually required for larger tumors. | 18,762,695 |
Heterotopic ileal pancreas with lipoma and coexisting fibromatosis associated with a rare case of gastrointestinal bleeding. A case report and review of the literature. | The development of pancreatic tissue outside the confines of the main gland represents a congenital abnormality referred to as heterotopic pancreas. This is a rare pathological and surgical entity which remains mostly asymptomatic. We present the case of a 28-year-old male, who was admitted to hospital because of a history of blood in bowel movements. After a normal gastroscopy and colonoscopy, Tc99m-tagged red blood cells scintigraphy showed enrichment in the right lower abdomen. At double-balloon endoscopy, a intraluminal polypoid mass 8 cm in diameter was revealed 120 cm from the ileocecal valve. The initial macroscopic diagnosis was a gastrointestinal stromal tumor. During surgery, the diagnosis of heterotopic pancreas with lipoma and fibromatosis was made. To our knowledge this is the first case of ileal heterotopic pancreatic tissue and lipoma described to date in the literature. Ileal heterotopic pancreas is a rare entity with potentially life-threatening complications, local excision being the appropriate indicated treatment. | 18,762,696 |
Impact of genetic polymorphisms of transporters on the pharmacokinetic, pharmacodynamic and toxicological properties of anionic drugs. | As the importance of drug transporters in the clinical pharmacokinetics of drugs is recognized, genetic polymorphisms of drug transporters have emerged as one of the determinant factors to produce the inter-individual variability of pharmacokinetics. Many clinical studies have shown the influence of genetic polymorphisms of drug transporters on the pharmacokinetics and subsequent pharmacological and toxicological effects of drugs. The functional change in a transporter in clearance organs such as liver and kidney affects the drug concentration in the blood circulation, while that in the pharmacological or toxicological target can alter the local concentration at the target sites without changing its plasma concentration. As for the transporters for organic anions, some single nucleotide polymorphisms (SNPs) or haplotypes occurring with high frequency in organic anion transporting polypeptide (OATP) 1B1, multidrug resistance 1 (MDR1), and breast cancer resistance protein (BCRP) have been extensively investigated in both human clinical studies and in vitro functional assays. We introduce some examples showing the relationship between haplotypes in transporters and pharmacokinetics and pharmacological effects of drugs. We also discuss how to predict the effect of functional changes in drug transporters caused by genetic polymorphisms on the pharmacokinetics of drugs from in vitro data. | 18,762,709 |
L-type fatty acid binding protein transgenic mouse as a novel tool to explore cytotoxicity to renal proximal tubules. | A novel biomarker of renal dysfunction, liver-type fatty acid binding protein (L-FABP), which is expressed in human proximal tubules, binds to lipid peroxidation products during renal injury and is excreted into the urine. Here, we examined the usefulness of human L-FABP transgenic (Tg) mice as a tool to explore nephrotoxicity, employing two model drugs, cephaloridine and cisplatin, which are taken up by renal tubules via organic anion and cation transporters, respectively. Urinary excretion of L-FABP increased after administration of cephaloridine in most of the Tg mice, whereas glomerular filtration markers such as blood-urea-nitrogen (BUN) and plasma creatinine (CRE) were almost unchanged. Thus, L-FABP is a highly sensitive detector of the nephrotoxicity of cephaloridine. Urinary excretion of L-FABP in the Tg mice also increased after administration of cisplatin, and this increase was reduced by coadministration of cimetidine. Both BUN and CRE also increased after the cisplatin treatment, but these parameters were minimally affected by coadministration of cimetidine, suggesting that cimetidine reduces cisplatin-induced renal tubular toxicity with only a minimal effect on the glomerulus. These results indicate that the L-FABP Tg mouse should be a useful drug screening system to evaluate specifically the toxicity of transporter substrates to renal tubules. | 18,762,714 |
Role of Na+/L-carnitine transporter (OCTN2) in renal handling of pivaloylcarnitine and valproylcarnitine formed during pivalic acid-containing prodrugs and valproic acid treatment. | Pivalic acid and valproic acid decreases L-carnitine concentration in the body via urinary excretion of their acylcarnitines, pivaloylcarnitine (PC) and valproylcarnitine (VC). To obtain an information about the mechanism of the physiological response, we investigated the renal handling of these acylcarnitines by Na+/L-carnitine cotransporter, OCTN2 using the isolated perfused rat kidney, rat OCTN2 (rOCTN2) and human OCTN2 (hOCTN2) expressing cells. In the perfused rat kidney, PC and VC were strongly reabsorbed with an efficiency comparable to L-carnitine, and these reabsorption were inhibited by 1 mM L-carnitine, suggesting that the interaction of L-carnitine with PC and VC reabsorption would be responsible for renal handling of these acylcarnitines in rats. The rOCTN2-mediated uptake of PC was lower than that of L-carnitine, whereas rOCTN2-mediated uptake of VC was as high as that of L-carnitine, indicating that contribution of rOCTN2 in renal handling of PC and VC would be different. Furthermore, hOCTN2-mediated uptake of these acylcarnitines was markedly lower than that of L-carnitine. On the other hand, both PC and VC inhibited L-carnitine reabsorption in the perfused rat kidney and their concentration-dependent inhibition was also observed for rOCTN2 and hOCTN2. These results suggest that low renal reabsorption and interaction of hOCTN2 for these acylcarnitines might possibly affect the decrease of L-carnitine concentration in humans. | 18,762,717 |
The effects of prolactin and gonadotropin on luteal function and morphology in the cyclic golden hamster. | The present study was conducted to evaluate the endocrinological effects of the pituitary on luteal maintenance and regression in the cyclic golden hamster (Mesocritus auratus). After hypophysectomy (Hypox) at 0900 h on day 1 of the estrous cycle (the day of ovulation), the animals received injection of prolactin (PRL) or PRL plus equine chorionic gonadotropin (eCG). They were decapitated at 1500 h on day 3 of the cycle, and trunk blood was collected for measurement of progesterone (P4). Corpora lutea (CLs) were dissected from one ovary for DNA ladder detection by electrophoresis, determination of DNA fragmentation ratio by fluorometric measurement method and measurement of P4. The other ovary was used for histological observation. After the Hypox, the daily injection of 1 mg ovine PRL restrained the DNA fragmentation ratio and number of apoptotic cell in the CLs. The PRL treatment maintained the luteal morphology and increased the luteal P4 concentration, but not in the plasma P4 concentration. In addition to PRL, injection of 2 IU eCG after the Hypox also restrained the DNA fragmentation ratio and number of apoptotic cells in the CLs to the level of a pregnant animal. The PRL plus eCG treatment maintained the luteal morphology in the same manner as the PRL only treatment and increased not only the luteal but also the plasma P4 concentration. These results suggest that PRL restrains luteal apoptosis and maintains luteal morphology and that the combination of PRL and eCG restrains not only structural but also functional luteal regression in the cyclic hamster. | 18,762,720 |
Lack of association between the dopamine transporter gene 3' VNTR polymorphism and attention deficit hyperactivity disorder in Chinese Han children: case-control and family-based studies. | Attention deficit hyperactivity disorder (ADHD) is the most common childhood onset neurodevelopment disorder. The etiology is unclear, but is suspected to involve the dopamine system. In this study we used the haplotype-based haplotype relative risk (HHRR) analysis and the transmission disequilibrium test (TDT) to investigate the potential contribution of dopamine transporter (DAT1) gene variants to ADHD. DAT1 gene polymorphisms were assessed in 54 ADHD Chinese Han children and all 108 of their parents and 66 normal child controls. No differences were found in either genotype or allele distributions. The HHRR analysis of the DAT1 polymorphisms suggests that the transmission of this polymorphism is not significantly associated with ADHD. And the TDT result showed that ADHD was not in linkage with the DAT1 gene. These findings do not support the hypothesis that DAT1 gene variants contribute to the pathogenesis of ADHD in Chinese Han population. | 18,762,727 |
Reversal effects of Ca2+ antagonists on multidrug resistance via down-regulation of MDR1 mRNA. | In previous reports, the effects of 12 Ca2+ antagonists on a multidrug resistant transporter, P-glycoprotein/MDR1, were evaluated in terms of those on MDR1-mediated transport of [3H]digoxin and the sensitivity of vinblastine sulfate or paclitaxel, and they were able to be classified into 4 subgroups based on their actions, as those with transport inhibition and sensitivity recovery, those with or without transport inhibition but marginal sensitivity recovery, and those without both. In this study, our previous findings were confirmed by the resistance against doxorubicin hydrochloride and daunorubicin hydrochloride, and by the recovery of [3H] vinblastine sulfate accumulation. Furthermore, it was found that the effects of 12 Ca2+ antagonists on the sensitivity recovery were also explained by the down-regulation of MDR1 mRNA, suggesting a novel mechanism to reverse the MDR1-mediated multidrug resistance. | 18,762,730 |
Acute effects of angiotensin II receptor blocker on ventricular repolarization alternans in chronic heart failure. | Repolarization alternans, which can be detected clinically as microvolt-level T-wave alternans (TWA), is considered an important mechanism underlying the initiation of ventricular tachycardia/ventricular fibrillation (VT/VF) linked to sudden cardiac death (SCD). Recently, the rennin-angiotensin system (RAS) inhibitors have been suggested to have potential benefits in reducing SCD as well as heart failure death with chronic heart failure (CHF). In this study, we tested the acute effects of an angiotensin II receptor blocker (ARB), valsartan, on the development of TWA and the heart rate at which TWA appeared (onset heart rate; OHR). Fifty consecutive patients with CHF underwent TWA measurement. Patients with positive TWA were administered valsartan (80 mg/day) orally for 3 days. Alternans voltage in the vector magnitude lead (Valt) and the OHR were compared before and after the drug exposure. TWA was positive in 19 patients (38%), negative in 16 (32%), and indeterminate in 15 (30%). Nineteen patients with positive TWA received valsartan. However, 3 patients were withdrawn due to adverse drug reactions. In all the remaining 16 patients, markedly reduced Valt (6.1 +/- 3.8 microV to 2.5 +/- 1.9 microV; P = 0.002) and increased OHR (94 +/- 9 beats/min to 102 +/- 9 beats/min; p = 0.002) were observed. In particular, 3 patients became TWA negative. These results suggest that the RAS inhibitors prevent SCD by the improvement of repolarization abnormality. | 18,762,731 |
The International Classification of Functioning Disability and Health: its development process and content validity. | The World Health Organization's International Classification of Functioning, Disability and Health (ICF) has provided a new foundation for our understanding of health, functioning, and disability. However, different challenges have to be addressed during its implementation process. The objective of this paper is to address two of these challenges, namely, the study of the content validity of the ICF and its relationship to other health-related concepts such as well-being, quality of life (QoL) and health-related quality of life (HRQoL). Ongoing validation studies confirm that the ICF is an exhaustive classification, i.e. it covers most of the health and health-related domains that make up the human experience of functioning and disability, and the most environmental factors that influence that experience of functioning and disability. The ICF also contributes to the understanding of health on a continuum ranging from a body-centred view (''the bodily experience of health''), to a more comprehensive perspective (''the entire health experience''), and finally, to an overarching view (''the human experience'') which sees health as part of the human condition. The ICF allows the operationalization of health as part of the human experience on this continuum as health from a narrow perspective to the broad perspective of functioning. The ICF with its categories can also serve as starting point for the operationalization of objective well-being. Since HRQoL can be defined as an individual's perceptions of health and health-related domains of well-being, the ICF categories encompassed in the ICF concept of functioning can also serve as the basis for the operationalization of HRQoL. | 18,762,740 |
Efficacy of imatinib mesylate in the treatment of refractory sclerodermatous chronic GVHD. | Treatment of sclerodermatous chronic GVHD (cGVHD) remains disappointing. Imatinib mesylate enables selective, dual inhibition of the transforming growth factor beta (TGFbeta) and PDGF pathways. Recently, the drug's effects on fibroblasts have been reported in both in vitro and in vivo studies. The inhibition of fibroblast growth and decreased collagen production in dermal fibroblasts is thus a logical therapeutic approach. Two patients who developed refractory sclerodermatous cGVHD following allo-SCT received imatinib mesylate at the dose of 400 mg/day. In both patients, the scleroderma symptoms disappeared within 3 months of initiation of the treatment. At the time of this report, the two patients were both alive and had a very good skin response. This report shows that imatinib is effective in patients with refractory sclerodermatous cGVHD. Considering its well-documented clinical profile in other diseases, imatinib is a promising candidate for the treatment of sclerodermatous cGVHD. | 18,762,765 |
Lapatinib therapy for patients with advanced renal cell carcinoma. | Lapatinib is an oral dual inhibitor of EGFR and HER2, the coexpression of which is associated with metastatic disease in patients with renal cell carcinoma. A recent randomized phase III trial of lapatinib versus hormone therapy was conducted in patients with cytokine-refractory metastatic renal cell carcinoma and tumors overexpressing EGFR and/or HER2. The study included 416 such patients who received either lapatinib (n = 209) or hormone therapy (n = 207). No benefit in time to progression, which was the primary end point of the study, or other clinical outcome measures, could be demonstrated for lapatinib therapy. A nonsignificant numerical advantage in time to progression was observed in patients with EGFR overexpression in the primary tumor (immunohistochemistry score 3+), suggesting that lapatinib could be of benefit in this subset of patients. This commentary emphasizes the need for further prospective studies to demonstrate the benefit of lapatinib therapy in patients with metastatic renal cell carcinoma. | 18,762,792 |
The atypical Rho GTPase RhoBTB2 is required for expression of the chemokine CXCL14 in normal and cancerous epithelial cells. | The Rho family of small GTPases control cell migration, cell invasion and cell cycle. Many of these processes are perturbed in cancer and several family members show altered expression in a number of tumor types. RhoBTB2/DBC2 is an atypical member of this family of signaling proteins, containing two BTB domains in addition to its conserved Rho GTPase domain. RhoBTB2 is mutated, deleted or silenced in a large percentage of breast and lung cancers; however, the functional consequences of this loss are unclear. Here we use RNA interference in primary human epithelial cells to mimic the loss of RhoBTB2 seen in cancer cells. Through microarray analysis of global gene expression, we show that loss of RhoBTB2 results in downregulation of CXCL14-a chemokine that controls leukocyte migration and angiogenesis, and whose expression is lost through unknown mechanisms in a wide range of epithelial cancers. Loss of RhoBTB2 expression correlates with loss of CXCL14 secretion by head and neck squamous cell carcinoma cell lines, whereas reintroduction of RhoBTB2 restores CXCL14 secretion. Our studies identify CXCL14 as a gene target of RhoBTB2 and support downregulation of CXCL14 as a functional outcome of RhoBTB2 loss in cancer. | 18,762,809 |
Osteogenic differentiation of rat mesenchymal stem cells from adipose tissue in comparison with bone marrow mesenchymal stem cells: melatonin as a differentiation factor. | Adipose-derived stem cells (ADSC) could be an appealing alternative to bone marrow stem cells (BMSC) for engineering cell-based osteoinductive grafts. Meanwhile, prior studies have demonstrated that melatonin can stimulate osteogenic differentiation. Therefore, we assayed and compared the melatonin effect on osteogenic differentiation of BMSC with that of ADSC. Mesenchymal stem cells (MSC) were isolated from the bone marrow and fat of adult rats. Both cell types were cultured in osteogenic medium in the absence and presence of melatonin at physiological concentrations (20-200 pg/ml). After 4 weeks, the expression of osteocalcin gene was analyzed by reverse transcription-PCR, alkaline phosphatase (ALP) activity was assayed and alizarin red S and von Kossa staining were done. Cell viability and apoptosis were also assayed by 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide, a tetrazole (MTT) and flow cytometry, respectively. The osteoblastic differentiation of ADSC as demonstrated by ALP activity was less than that of BMSC. The amount of matrix mineralization has shown by alizarin red S and von Kossa staining also showed statistical differences between the two MSC. The incidence of apoptotic cells was higher among ADSC than BMSC. The flow cytometry proves that cell growth reduction is due to a decrease in the number of the cells entering the S phase of the cell cycle. MTT assay indicated that viable cells were fewer among ADSC than BMSC in control groups. The results of the study suggest that BMSC have greater osteogenic potential than ADSC and that melatonin promotes osteogenic differentiation to BMSC, but has a negative effect on ADSC osteogenic differentiation. | 18,762,816 |
The chemistry of gold as an anion. | Due to relativistic and classical shell structure effects, the 6s orbital of gold is significantly contracted and energetically stabilized. This is reflected by a strikingly high electron affinity, and a distinct tendency to adopt negatively polarized valence states. This tutorial review focuses on the chemistry of gold as an anion, displaying the integral ionic charge number of 1-. Two synthetic approaches to compounds containing monoatomic gold anions have become available: (1) reacting elemental gold with molten caesium and an oxide, e.g. Cs2O; (2) metathesis reactions involving Au- dissolved in liquid ammonia. Both procedures have proven to be rather versatile. Aurides synthesized along these routes are surveyed, in particular with respect to their structures and bonding properties. | 18,762,832 |
The use of gold nanoparticles in diagnostics and detection. | The widespread use of gold nanoparticles (GNPs) as labels in diagnostics and detection is due to a unique combination of chemical and physical properties that allow biological molecules to be detected at low concentrations. In this critical review detection methods based on GNPs are divided up and discussed based on the way in which signals are generated in response to specific target molecules. Particular attention is devoted to methods that allow target molecules to be detected with the unaided eye because these, more than any other, harness the full range of properties that make GNPs unique. Methods that are discussed include those in which specific target molecules induce a visible colour change, chromatographic methods that allow non-specialized users to perform sophisticated tests without additional equipment and methods in which trace amounts of GNPs are rendered visible to the unaided eye by catalytic deposition of a metal such as silver. The use of metal deposition as a means of enhancing the signal for optical and electrical detection is also reviewed. The other detection methods included in this review are based on interactions between GNPs and molecules located in close proximity to their surface. These include methods in which light emission from such molecules is enhanced (surface enhanced Raman scattering) or quenched (fluorescence), and methods in which the accumulation of specific target molecules induce subtle changes in the extinction spectra of GNPs that can be followed in real time with inexpensive equipment (166 references). | 18,762,845 |
Supported gold nanoparticles as catalysts for organic reactions. | This critical review is intended to attract the interest of organic chemists and researchers on green and sustainable chemistry on the catalytic activity of supported gold nanoparticles in organic transformations. In the general part of this critical review, emphasis is given to the different procedures to form supported gold nanoparticles and to the importance of the support cooperating in the catalysis. Also the convergence of homogeneous and heterogeneous catalysis in the study of gold nanoparticles has been discussed. The core part of this review is constituted by sections in which the reactions catalyzed by supported gold nanoparticles are described. Special emphasis is made on the unique ability of gold catalysts to promote additions to multiple C-C bonds, benzannulations and alcohol oxidation by oxygen (282 references). | 18,762,848 |
Catalysis by gold dispersed on supports: the importance of cationic gold. | There are many examples of catalysis in solution by cationic complexes of gold, and recent results, reviewed here in this critical review, demonstrate that cationic gold species on oxide and zeolite supports are also catalytically active, for reactions including ethylene hydrogenation and CO oxidation. The catalytically active gold species on supports are evidently not restricted to isolated mononuclear gold complexes, but include gold clusters, which for at least some reactions are more active than the mononuclear complexes and for some reactions less active. Fundamental questions remain about the nature of cationic gold in supported catalysts, such as the nature of the cationic gold clusters and the nature of gold atoms at metal-support interfaces (88 references). | 18,762,849 |
A simple method for amino acid selective isotope labeling of recombinant proteins in E. coli. | A simple and user-friendly method of labeling protein selectively with amino acids in vivo is introduced. This technique does not require the use of transaminase-deficient or auxotrophic strains. By manipulating the product feedback inhibitory loops of the E. coli amino acid metabolic pathways and, if necessary, by using enzyme inhibitors, proteins were labeled efficiently in vivo even with amino acid types that are central to the metabolic pathways, such as glutamine. The sequential backbone resonance assignment of the Neh2 domain of Nrf2 transcriptional factor, an intrinsically disordered protein with high spectral degeneracy, was achieved using this labeling method. | 18,762,866 |
Characterization of S1 nuclease sensitive site at transcription initiation region of Attacus ricini rDNA. | A single-stranded S1 nuclease hypersensitive site which contains a d(AT)(18) sequence structure located in the 5'-non transcription spacer of silkworm A. ricini ribosomal RNA gene has been reported([1]). Using starved-refed silkworms, another S1 nuclease sensitive site was found existing in the rDNA chromatin, while under merely starving, this S1 sensitive site disappeared([2]). Recently this inducible S1 sensitive site has been further determined. It consists of a d(GT)(10)-d(AT)(10) special DNA sequence at the transcription initiation region, and shows a behavior of ease in DNA-unwinding, indicating that S1 nuclease sensitive sites may have an important function in the regulation of rDNA transcription and replication. | 18,762,880 |
Simultaneous bilateral opening-wedge high tibial osteotomy with early full weight-bearing exercise. | Simultaneous bilateral opening-wedge high tibial osteotomies (OWHTOs), using the TomoFix fixation device and artificial bone wedges (beta-TCP) were performed on 20 knees of 10 patients with an average age of 67 years (range 53-75) at the time of the operation. We established an early weight-bearing exercise program during which patients were permitted partial weight-bearing exercise 1 week after osteotomy, with all patients performing full weight-bearing exercise at 3 weeks. The follow-up period was an average of 15 months (range 6-39). The American Knee Society Score and the Function Score were improved significantly from 46 +/- 8.1 to 92 +/- 6.8 points and 67 +/- 7.9 to 95 +/- 7.9 points, respectively. Prior to surgery, the average lateral femoro-tibial angle (FTA) during standing was 182 +/- 2.3 degrees (2 degrees anatomical varus) and significantly changed to 170 +/- 2.5 degrees (10 degrees valgus) at the time of follow-up. There were no cases of infection, non-union, or implant failure. Overall, this procedure was highly successfully in correcting knee malalignment in patients with medial compartmental osteoarthritis. In our study also, there was no evidence of correction loss, implant failure, collapse of the artificial bone wedges, or screw loosening. Simultaneous treatment of bilateral OWHTOs under a single administration of anesthesia appears to be superior to separate procedures of unilateral surgical procedures in providing the potential benefits of minimizing hospitalization, reducing costs and maximizing clinical outcomes for patients and institutions. | 18,762,910 |
Comparison of the bioabsorbable and metal screw fixation after ACL reconstruction with a hamstring autograft in MRI and clinical outcome: a prospective randomized study. | There has never been an MRI study of tunnel widening comparing bioabsorbable to metal screw fixation in autologous hamstring anterior cruciate ligament (ACL) reconstruction. We randomized 62 patients to hamstring ACL reconstruction with either a bioabsorbable (n=31) or metal screw (n=31) fixation. The evaluation methods were clinical examination, KT-1000 arthrometric measurement, the International Knee Documentation Committee and Lysholm scores, and MRI. There were no differences between the groups preoperatively. Fifty-five patients (89%) were available at a minimum of 2-year follow-up (range 24-36 months). There was tunnel widening in both groups, but the increase was significantly greater in the AP dimension of the femoral tunnel in the bioabsorbable screw group compared to metal group (P=0.01). The tibial tunnels showed no intergroup difference. Ninety-four percent of the knees were normal or nearly normal according to the IKDC scores and the average Lysholm score was 91 with no intergroup difference. The follow-up AP tibial tunnel diameter was smaller with normal knee laxity compared to abnormal knee laxity. The graft failure rate in the bioabsorbable screw group was 23% (7/31 patients) and 6% (2/31 patients) in the metal screw group. The use of bioabsorbable screws resulted in more femoral tunnel widening, and more graft failures compared to metal screws. The tunnel widening in the tibia was associated with the knee laxity (P=0.02). | 18,762,911 |
Cross-modal plasticity for the spatial processing of sounds in visually deprived subjects. | Until only a few decades ago, researchers still considered sensory cortices to be fixed or "hardwired," with specific cortical regions solely dedicated to the processing of selective sensory inputs. But recent evidences have shown that the brain can rewire itself, showing an impressive range of cross-modal plasticity. Visual deprivation is one of the rare human models that allow us to explore the role of experience-dependent plasticity of a sensory cortex deprived of its natural inputs. The objective of this paper is to describe recent results regarding the spatial processing of sounds in blind subjects. These studies suggest that blind individuals may demonstrate exceptional abilities in auditory spatial processing and that such enhanced performances may be intrinsically linked to the recruitment of occipital areas deprived of their normal visual inputs. Such results highlight the brain's remarkable ability to rewire its components to compensate for the challenging neurological condition that is visual deprivation. Moreover, we shall discuss that such cross-modal recruitment may, to some extent, follow organizational principles similar to the functional topography of the region observed in the sighted. Even if such recruitment is especially present in individuals having lost their sight in early infancy, occipital regions also show impressive plastic properties when vision is lost at a later age. This observation will be related to recent results demonstrating that occipital regions play a more important role than previously expected in the spatial processing of sounds, even in sighted subjects. Putative physiological mechanisms underlying such cross-modal recruitment will then be discussed. All these results have important implications for understanding the role of visual experience in shaping the development of occipital regions and may guide the implementation of rehabilitative methods such as sensory substitution or neural implants. | 18,762,928 |
Non-classical hereditary hemochromatosis in Portugal: novel mutations identified in iron metabolism-related genes. | The most frequent genotype associated with Hereditary hemochromatosis is the homozygosity for C282Y, a common HFE mutation. However, other mutations in HFE, transferrin receptor 2 (TFR2), hemojuvelin (HJV) and hepcidin (HAMP) genes, have also been reported in association with this pathology. A mutational analysis of these genes was carried out in 215 Portuguese iron-overloaded individuals previously characterized as non-C282Y or non-H63D homozygous and non-compound heterozygous. The aim was to determine the influence of these genes in the development of iron overload phenotypes in our population. Regarding HFE, some known mutations were found, as S65C and E277K. In addition, three novel missense mutations (L46W, D129N and Y230F) and one nonsense mutation (Y138X) were identified. In TFR2, besides the I238M polymorphism and the rare IVS5 -9T-->A mutation, a novel missense mutation was detected (F280L). Concerning HAMP, the deleterious mutation 5'UTR -25G-->A was found once, associated with Juvenile Hemochromatosis. In HJV, the A310G polymorphism, the novel E275E silent alteration and the novel putative splicing mutation (IVS2 +395C-->G) were identified. In conclusion, only a few number of mutations which can be linked to iron overload was found, revealing their modest contribution for the development of this phenotype in our population, and suggesting that their screening in routine diagnosis is not cost-effective. | 18,762,941 |
Protective effect of trapidil on long-term histologic damage in a rat model of testicular ischemia-reperfusion injury. | Trapidil is an antianginal compound with a broad spectrum of pharmacological activities. In recent years, it has been used successfully to decrease ischemia-reperfusion injury in several organ systems. We evaluated the effect of trapidil on the long-term histologic damage in testicular ischemia-reperfusion injury. Adult male Wistar rats were divided into three groups of six rats each. One group underwent 2 h of testicular torsion; one received pretreatment with trapidil before detorsion; and one group underwent sham operation. All rats underwent bilateral orchiectomy 60 days after the experiment. The mean seminiferous tubular diameter, germinal epithelial cell thickness, and mean testicular biopsy score were determined by histological examination of each testis. Testicular torsion-detorsion caused a significant decrease in the mean seminiferous tubular diameter, germinal epithelial cell thickness, and mean testicular biopsy score in the ipsilateral testes, but not in the contralateral testes. The animals treated with trapidil had a significant increase in these histological parameters as compared to the torsion-detorsion group. Trapidil administration before reperfusion may have the potential to decrease the long-term histologic damage that occurs after experimental testicular torsion. Trapidil is used as an antianginal drug and additional clinical studies are required to elucidate the protective role of trapidil in patients with testicular torsion. | 18,762,946 |
Activation of big conductance Ca(2+)-activated K (+) channels (BK) protects the heart against ischemia-reperfusion injury. | Activation of the large-conductance Ca(2+)-activated K(+) channel (BK) in the cardiac inner mitochondrial membrane has been suggested to protect the heart against ischemic injury. However, these findings are limited by the low selectivity profile and potency of the BK channel activator (NS1619) used. In the present study, we address the cardioprotective role of BK channels using a novel, potent, selective, and chemically unrelated BK channel activator, NS11021. Using electrophysiological recordings of heterologously expressed channels, NS11021 was found to activate BK alpha + beta1 channel complexes, while producing no effect on cardiac K(ATP) channels. The cardioprotective effects of NS11021-induced BK channel activation were studied in isolated, perfused rat hearts subjected to 35 min of global ischemia followed by 120 min of reperfusion. 3 microM NS11021 applied prior to ischemia or at the onset of reperfusion significantly reduced the infarct size [control: 44.6 +/- 2.0%; NS11021: 11.4 +/- 2.0%; NS11021 at reperfusion: 19.8 +/- 3.3% (p < 0.001 for both treatments compared to control)] and promoted recovery of myocardial performance. Co-administration of the BK-channel inhibitor paxilline (3 microM) antagonized the protective effect. These findings suggest that tissue damage induced by ischemia and reperfusion can be reduced by activation of cardiac BK channels. | 18,762,970 |
Evaluation of the relative importance of chemotherapeutic and antiemetic efficacy in various oncologic settings. | This study investigated physician's attitudes toward the relative importance of chemotherapeutic and antiemetic efficacy in different clinical scenarios. Oncologists in the USA and four European countries completed an online stated-choice survey consisting of three hypothetical treatment choices for each of two patient types. Each hypothetical treatment alternative included both chemotherapy and antiemetic regimens. The two hypothetical patient types were (1) a 48-year-old woman with locoregional infiltrating ductal carcinoma of the breast and (2) a 78-year-old man with squamous cell carcinoma of the lung and multiple liver metastases. In each choice question, oncologists were asked to select the better combination of chemotherapy and antiemetic prophylaxis between two treatment alternatives. Five hundred fifty-seven oncologists completed the survey. For the adjuvant breast cancer patient, the most aggressive chemotherapy is consistently the most important treatment consideration in all countries. For the advanced lung cancer patient, the most aggressive chemotherapy, the less aggressive chemotherapy, and the most aggressive antiemetic prophylaxis are of similar importance in most countries. Physicians appear more likely to prescribe a more aggressive chemotherapy regimen for a younger patient with a perceived curable tumor, regardless of the emetogenic properties of the chemotherapy. Symptom management is more of a concern and chemotherapeutic efficacy relatively less of a priority in an older patient with advanced disease for whom chemotherapy is not curative. | 18,762,991 |
Proinflammatory cytokine gene polymorphisms among Iranian patients with asthma. | Asthma is one of the most common respiratory diseases caused by acute and chronic inflammation of airways. Proinflammatory cytokines could contribute to this inflammatory process. This study was performed in order to analyze the genetic profile of proinflammatory cytokines in Iranian asthmatic patients. The allele and genotype frequencies of a number polymorphic genes coding for tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 alpha, IL-1 beta, IL-1 receptor (IL-1R), IL-1RA, and IL-6 were investigated in 60 patients with asthma in comparison with 140 controls using polymerase chain reaction with sequence-specific primers. The most frequent genotypes in our patients were TNF-alpha GA at position -308 (P = 0.001), TNF-alpha AA at position -238 (P = 0.01), IL-1 alpha TC at position -889 (P = 0.0001), IL-1 beta TC at position -511 (P = 0.0001), and IL-1RA TC at position Mspa-I 11100 (P = 0.001). In contrast, the frequencies of the genotypes TNF-alpha GG at position -308 (P = 0.001), IL-1 alpha CC at position -889 (P = 0.005), IL-1 beta CC at position -511 (P = 0.0001), and IL-1RA TT at position Mspa-I 11100 (P = 0.0001) in the patient group were significantly lower than controls. The most frequent haplotypes for TNF-alpha (positions 308, -238) was A/A in the patient group in comparison with controls (P = 0.0001). While environmental factors are important in the development of asthma, genetic factors could have a critical role in the expression of the disease. Considering the high frequency of presence of TNF-alpha AG genotype (-308), it seems that the production of TNF-alpha in the asthmatic patients could be higher than normal subjects. | 18,763,028 |
Family history is a significant risk factor for pancreatic cancer: results from a systematic review and meta-analysis. | Epidemiologic evidence suggests a family history of pancreatic cancer (PC) is a risk factor for the disease, yet the magnitude of risk varies between studies. We performed a systematic review of studies that quantified familial risks of PC, and through a meta-analysis, obtained more precise estimates of familial risk. A MEDLINE search identified published studies that reported relative risks (RR) of PC associated with a family history of the disease. A random effects model was used to summarize study-specific RRs and 95% confidence intervals (CI). Sensitivity and sub-group analyzes were performed. Seven case-control and two cohort studies involving 6,568 PC cases were identified. There was no evidence of statistical heterogeneity between studies (I(2) = 0%; P = 0.483). Results from case-control (RR = 2.82; 95% CI: 1.99-3.66) and cohort (RR = 1.62; 95% CI: 1.28-1.97) studies showed a significant increase in PC risk associated with having an affected relative, with an overall summary RR = 1.80 (95% CI: 1.48-2.12). Similar RR were observed for early (RR = 2.69; 95% CI: 0.56-4.82) and later (RR = 3.41; 95% CI: 0.79-6.03) onset disease in the index case. Data was too sparse to generate an overall summary RR based on the number or type of affected relatives. Individuals with a family history of PC have nearly a two-fold increased risk for developing PC compared to those without such a history. Families with two or more PC cases may benefit from comprehensive risk assessment that involves collection of detailed family history information and data regarding various risk factors for PC, especially smoking history. Those at highest risk may be referred to screening programs and studies; these are important steps toward early detection and greater odds of surviving this disease. | 18,763,055 |
Heat-shock response protects peripheral blood mononuclear cells (PBMCs) from hydrogen peroxide-induced mitochondrial disturbance. | The present study was designed to investigate ex vivo the protective mechanisms of heat-shock response against H(2)O(2)-induced oxidative stress in peripheral blood mononuclear cells (PBMCs) of rats. Twenty-four hours later, heat-shock treatment was executed in vivo; rat PBMCs were collected and treated with H(2)O(2). The accumulation of reactive oxygen species and the mitochondrial membrane potential were evaluated by intracellular fluorescent dHE and JC-1 dye staining, respectively, and expression of HSP72 and cytochrome c was detected by Western blot analysis. Cellular apoptosis was assayed by TUNEL staining and double staining of Annexin V and PI. The results showed that H(2)O(2)-induced oxidative stress leads to intracellular superoxide accumulation and collapse of the mitochondrial membrane potential in rat PBMCs. Moreover, cellular apoptosis was detected after H(2)O(2) treatment, and the release of mitochondrial cytochrome c from mitochondria to cytosol was significantly enhanced. Heat-shock pretreatment decreases the accumulation of intracellular superoxide in PBMCs during H(2)O(2)-induced oxidative stress. Moreover, heat-shock treatment prevents the collapse of the mitochondrial membrane potential and cytochrome c release from mitochondria during H(2)O(2)-induced oxidative stress. In conclusion, mitochondria are critical organelles of the protective effects of heat-shock treatment. Cellular apoptosis during H(2)O(2)-induced oxidative stress is decreased by heat-shock treatment through a decrease in superoxide induction and preservation of the mitochondrial membrane potential. | 18,763,057 |
Molecular mechanism of signaling by tumor necrosis factor. | Tumor necrosis factor (TNF) is an important cytokine with multiple biological effects, including cell growth, differentiation, apoptosis, immune regulation and induction of inflammation. The effects of TNF are mediated by two receptors, TNF-R1 and TNF-R2. The major signal transduction pathways triggered by TNF include those that lead to apoptosis, activation of transcription factor NF-kappa B and protein kinase JNK. This review will discuss the molecular mechanisms of these signaling pathways. | 18,763,070 |
Opening angles and residual strains in normal rat trachea. | The no-load state and zero-stress state of the normal rat trachea were analyzed. It was found that there exist compressive residual strains in the inner wall region of the rat trachea and tensile residual strains in the outer wall region. The fact that the opening angle of the rat trachea cut at the cartilaginous region is significantly larger than that cut at the muscular portion shows that residual strains exist mainly in the muscular region in the rat trachea. It was also indicated that the opening angles and residual strains expressed by cutting at the muscular portion are basically identical along longitudinal location and those expressed by cutting in the cartilaginous region tend to increase in the longitudinal direction in the normal rat, and that there exists quantitatively positive correlation between the opening angles and residual strains in rat trachea. The results will help to further understand the opening angles and residual strains in the trachea and study tracheal remodeling in response to mechanical environment. | 18,763,073 |
Amylin evokes protein p20 phosphorylation and insulin resistance in rat skeletal muscle extensor digitorum longus. | In the present study, we investigate effect of amylin on the insulin sensitivity of rat skeletal muscle extensor digitorum longus (EDL) using in vitro intact muscle incubation in combination with metabolic radioactive labeling. The molecular basis of the amylin action was further examined using proteomic analysis. In particular, proteins of interest were characterized using an integrated microcharacterization procedure that involved in-gel trypsin digestion, organic solvent extraction, high performance liquid chromatography separation, microsequencing and microsequence analysis. We found that amylin significantly decreased the insulin-stimulated glucose incorporation into glycogen (p < 0.01) and produced a protein spot of approximately 20 ku in size. This amylin responsive protein (hereby designated as amylin responsive protein 1, APR1) was identified to be protein p20. Moreover, ARP1 spots on gels were found to consistently produce a corresponding radioactive spot on X-ray films in (32)Pi but not in (35)S-methionine labeling experiments. In conclusion, our results showed that in vitro amylin concomitantly evoked the production of ARP1 and caused insulin resistance in EDL muscle. It is suggested that protein p20 may be involved in amylin signal transduction and the appearance of ARP1 may be a step in a molecular pathway leading to the development of insulin resistance. ARP1 might therefore be a useful molecular marker for amylin action, insulin resistance and Type 2 diabetes. | 18,763,075 |
Constitutive expression of human coagulating factor IX in HeLa cells by homologous recombination of the promoter. | Constitutive expression of hFIX protein in nonhepatocytes was studied. The gene targeting vector was constructed and transferred into HeLa cells. With the detection system of PCR, we demonstrated that the endogenoushFIX promoter was replaced with anhCMV promoter when targeted insertion of the constructor was directed by the sequence homology. The expression ofhFIX in the modified HeLa cells, 11.2 ng/10(6) cell/24 h, strongly suggested thathFIX gene could be activated by a powerful promoter in nonhepatocytes. The results would make it possible to examine the feasibility of re-regulate gene expression by promoter replacement. | 18,763,084 |
Binocular fusion in Panum's limiting case of stereopsis obeys the uniqueness constraint. | In the information processing procedure of stereo vision, the uniqueness constraint has been used as one of the constraints to solve the "correspondence problem". While the uniqueness constraint is valid in most cases, whether it is still valid in some particular stimulus configuration (such as Panum's limiting case) has been a problem of widespread debate for a long time. To investigate the problem, we adopted the Panum's limiting case as its basic stimulus configuration, and delved into the phenomenon of binocular fusion from two distinct aspects: visual direction and orientation disparity. The results show that in Panum's limiting case binocular fusion does not comply with the rules governing regular binocular fusion as far as visual direction and orientation disparity are concerned. This indicates that double fusion does not happen in Panum's limiting case and that the uniqueness constraint is still valid. | 18,763,087 |
Study of rat neuronal genes with ordered differential display method. | Ordered differential display (ODD) was developed recently and has been applied to systematic comparison of expression profiles of genes. It was further improved with the specific complexing property between biotin and streptavidin by the authors. First, random primer and biotinylated oligo (dT) primer were used to make pools of double strand cDNA. Second, streptavidin-coated PCR tube is used to absorb 3'ESTs specifically to avoid the negative effect of other DNA fragments. In the case of 3'ESTs comparison patterns between embryonic brain and body of SD rat, more than forty differentially expressed genes were cloned and identified. The function of rZIC gene, one of the genes identified and cloned, was studied through ethological experiments. The result showed that rZIC gene was associated with locomotion activity of adult mice. | 18,763,101 |
Activity identification of chimeric anti-caspase-3 mRNA hammerhead ribozyme in vitro and in vivo. | To study the expression activity of various vectors containing anti-caspase-3 ribozyme cassettes in vivo, and to further study the role of caspas-3 in the apoptotic pathway, we constructed anti-caspase-3 hammerhead ribozyme embedded into the human snRNA U6, and detected the activity of the ribozyme in vitro and in vivo. Meanwhile we compared it with the self-cleaving hammerhead ribozymes that we previously studied, and with the general ribozyme, cloned into RNA polymerase II expression systems. The results showed that the three ribozymes, p1.5RZ107, pRZ107 and pU6RZ107 had the correct structure, and that they could cleave caspase-3 mRNA exactly to produce two fragments: 143nt/553nt. p1.5RZ107 has the highest cleavage efficiency in vitro, almost 80%. However, the U6 chimeric ribozyme, pU6RZ107, has the highest cleavage activity in vivo, almost to 65%, though it has lower cleavage activity in vitro. The cleavage results demonstrated that the pU6RZ107, the U6 chimeric ribozyme, could more efficiently express and downregulate the level of caspase-3 in vivo, and the ribozyme could provide an alternative approach to the research into the mechanism of apoptosis and human gene therapy also. | 18,763,103 |
The uplift of Qinghai-Xizang (Tibet) Plateau and the vicariance speciation of glyptosternoid fishes (Siluriformes: Sisoridae). | Based on the phylogenetic and biogeographical studies of the glyptosternoid fishes in Qinghai-Tibet area, the following hypothesis is proposed: the speciation of this group has a direct relationship with the three uplift intervals of the Qinghai-Tibet Plateau. This process was explained by the theory of vicariance of biogeography. The ancestor of this group was similar to Bagarus and/or Glyptothorax, which still have a wide distribution. At the moment when the Tethys sea closed, the Indian tectonic plate collided with the Eurasian tectonic plate, so the Glyptothorax-like and Bagarus-like ancestors entered Eurasia and gradually became widely distributed. After the Pleistocene, with the enforced colliding, the gradual uplift of the Qinghai-Tibet Plateau brought about the current water environment, and the Glyptosternoids were generated from Glyptothorax-like fish under this environment. The present Glyptosternum, distributed across the Himalayas is the ancestor of Glyptosternoids. In the three uplift intervals of the plateau, the water system of this region was separated gradually and Glyptosternum-like ancestor was isolated in different rivers and evolved into various species. All this resulted in the speciation and formation of the biogeographical pattern of glyptosternoids. | 18,763,106 |
The human apoE7 and apoE4 transgenic mice models. | To scrutinize the disorders caused by human mutant apoE7/apoE4, human apoE4 and E7 transgenic mice were established with microinjection technique to examine molecular genetic phenomena in vivo. The integration and expression of h-apoE mutant genes in transgenic mice were determined with Southern blot, Northern blot and ELISA. The current studies indicated that the transgenes and the phenotypes regarding expression of transgenes could be transmitted stably in transgenic lines. The levels of serum lipid in transgenic mice showed the characteristics of hyperlipidemia. Besides, behavior tests demonstrated the degeneration of learning and memory in transgenic mice. Short life span was observed in 2 transgenic lines. After fed with high lipid food high serum lipid was found both in normal and transgenic mice, but their mechanism regulating lipid metabolism was different. It was also verified that the human apoE mutants located at either N-terminal or C-terminal had the same pathogenesis regarding disorders of lipid metabolism in murine. | 18,763,107 |
Effect of different immunosuppressive drugs on calcineurin and its mutants. | Several mutants in Loop7 region and near Loop7 region of calcineurin A (CN A) subunit have been constructed and purified using site-directed mutagenesis. Their phosphatase activity and the corresponding solution conformation were examined. Their phosphatase activities between wild-type CN and mutants were compared to identify the interaction of different immunosuppressive drugs with CN. The results showed that the phosphatase activities of the mutants at Loop7 were much higher than the one of wild-type CN. Furthermore, circular dichroism spectra of the mutants revealed that their solution conformations gave rise in changes in native structure of the protein. Cyclophilin-CyclosporinA (CyP-CsA) significantly inhibited the phosphatase activity of wild-type CN, and had no effects on the phosphatase activity of mutants in Loop7 region, which indicates that the site-directed mutagenesis at Loop7 region made a significant change in the interaction between CyP-CsA and CN. Examination of the activities of these mutants resulted in the presence of immunosuppressive component from traditional Chinese drugs. The component of Chinese drug, ZIP1, could directly inhibit both CN and CN mutants without drug binding protein. These results suggest that the Loop7 region is an important structural area involved in the inhibition by CyP-CsA. It is valuable to further study the inhibition by ZIP1. | 18,763,117 |
Structural feature of sorghum chloroplastpsbA gene and regulation effects of its 5'-noncoding region. | Comparative analysis reveals remarkahle homology between the sequences of bothpsbA gene nucleotides and the inferred amino acids of sorghum, a C(4) plant, and those of rice, a C(3) plant. The 5'-noncoding region of sorghumpsbA gene contains the conservative promoter elements, "-35" element and "-10" element, like the prokaryote and the promoter element, TATA box, like the eukaryote. As compared with that of the rice, an extra sequence of 7 bp is found in the leader sequence of the mRNA in the former. Using anin vitro system, it has been demonstrated that protein factor exists in sorghum chloroplast protein extract which specifically hinds to the 5'-noncoding region ofpsbA gene. Measurement of the expression of luciferase shows a 2-5 time greater reaction of the expression plasmids pALqs which contain leader region of sorghumpsbA gene than that of the expression plasmids pALqr which contain leader region of ricepsbA gene inE. coli. | 18,763,129 |
Effect of DNA binding protein Ssh12 from hyperthermophilic archaeonSulfolobus shibatae on DNA supercoiling. | An 11.5-ku DNA binding protein, designated as Ssh12, was purified from the hyperthermophilic archaeonSulfolobus shibatae by column chromatography in SP Sepharose, DNA cellulose and phosphocellulose. Ssh12 accounts for about 4 % of the total cellular protein. The protein is capable of binding to both negatively supercoiled and relaxed DNAs. Nick closure analysis revealed that Ssh12 constrains negative supercoils upon binding to DNA. While the ability of the protein to constrain supercoils is weak at 22 degrees C, it is enhanced substantially at temperatures higher than 37 degrees C. Both the cellular content and supercoil-constraining ability of Ssh12 suggest that the protein may play an important role in the organization and stabilization of the chromosome ofS. shibatae. | 18,763,131 |
ESI-MS study on non-covalent bond complex of rhFKBP12 and new neurogrowth promoter. | An ESI-MS method for studying the non-covalent bond complex of rhFKBP12 with its nonimmunosuppressive ligands was developed. The method was used to screen out three compounds capable of binding to rhFKBP12 non-covalently from 52 compounds. By competing binding experiment, the binding site and the relative binding strength of these three compounds 000107, 000308 and A2B12 with rhFKBP12 were measured. All of them have the same binding site as FK506 does. X-ray crystalline diffraction experiment of non-covalent bond complex of 000107, 000308 with rhFKBP12 by Tsinghua University showed the same results. Among them 000308 has good effect on stimulating neurite to grow in chicken sensory neuronal cultures. | 18,763,143 |
Effects of TFAR19 gene on the growth and biorheological properties of mouse erythroleukemia cell line MEL. | Using the method of gene transfection with liposome, we obtained the mouse erythroleukemia cell line MEL-TF19, which stably carries TFAR19, a novel apoptosis-related gene. The expression of TFAR19 was detected by Western blot. Growth curve and flow cytometry analysis showed that after being transfected with TFAR19 gene, the growth of MEL-TF19 is suppressed and its apoptosis is accelerated because of the serum deprivation. Our biorheological study indicated that in the apoptotic process, compared with MEL cells, MEL-TF19 cells exhibit larger osmotic fragility, lower cell surface charge density, increased elastic modulus K (1) which is inversely proportional to cells' maximal deformation ability, obviously diminished surface viscosity mu, with elastic modulus K (2)having no distinct changes. The above results provided some bases for recognizing the function of TFAR19 completely from the viewpoint of biorheology. | 18,763,144 |
Effects of simulated microgravity on nitric oxide level in cardiac myocytes and its mechanism. | The depression of cardiac contractility induced by space microgravity is an important issue of aerospace medicine research, while its precise mechanism is still unknown. In the present study, we explored effects of simulated microgravity on nitric oxide (NO) level, inducible nitric oxide synthase (iNOS) expression and related regulative mechanism using electron spin resonance (ESR) spectroscopy, immunocytochemistry and in situ hybridization. We found a remarkable increase of NO level and up-regulation of iNOS and iNOS mRNA expression in rat cardiac myocytes under simulated microgravity. Staurosporine (a nonselective protein kinase inhibitor), calphostin C (a selective protein kinase C inhibitor), partially inhibited the effect of simulated microgravity. Thus regulative effect of simulated microgravity on iNOS expression is mediated at least partially via activation of protein kinase C. These results indicate that NO system in cardiac myocytes is sensitive to simulated microgravity and may play an important role in the depression of cardiac contractility induced by simulated microgravity. | 18,763,145 |
Inhibition of human poly(A)-specific ribonuclease (PARN) by purine nucleotides: kinetic analysis. | Poly(A)-specific ribonuclease (PARN) is a cap-interacting and poly(A)-specific 3'-exoribonuclease that efficiently degrades mRNA poly(A) tails. Based on the enzyme's preference for its natural substrates, we examined the role of purine nucleotides as potent effectors of human PARN activity. We found that all purine nucleotides tested can reduce poly(A) degradation by PARN. Detailed kinetic analysis revealed that RTP nucleotides behave as non-competitive inhibitors while RDP and RMP exhibit competitive inhibition. Mg(2 + ) which is a catalytically important mediator of PARN activity can release inhibition of RTP and RDP but not RMP. Although many strategies have been proposed for the regulation of PARN activity, very little is known about the modulation of PARN activity by small molecule effectors, such as nucleotides. Our data imply that PARN activity can be modulated by purine nucleotides in vitro, providing an additional simple regulatory mechanism. | 18,763,168 |
Drug discovery and development for Huntington's disease - an orphan indication with high medical need. | Huntington's disease (HD) is a rare neurodegenerative disorder that progressively destroys the mental capacity and motor control of patients. This loss of motor control results in abnormal body movements (chorea) - the hallmark of HD. Given that no disease-modifying therapy for HD exists and that available symptomatic treatments are not highly efficacious, the medical need for this 'orphan' disease remains high. The number of compounds that are undergoing discovery and development for the treatment of HD has increased significantly in recent years, spurred by legislative incentives for orphan drug development and by support from non-profit foundations. Thus, hope exists for patients with HD that efficacious medicines will become available. | 18,763,216 |
Standardized remission criteria in schizophrenia: descriptive validity and comparability with previously used outcome measures. | Standardized consensus criteria for remission in schizophrenia were recently proposed. As yet, the validity of these criteria and their comparability with previously used outcome measures are unclear. The symptom-severity component of the proposed remission criteria was applied to 288 inpatients who fulfilled the ICD-10 criteria for schizophrenia. Global functioning and psychopathological symptoms were assessed using GAF, PANSS, SANS, HAM-D and CDSS. When patients with symptom remission at discharge from hospitalization (n=158, 54.9%) were compared to those without symptom remission, significant differences were found with respect to the global functioning (GAF) and all observed psychopathological symptom dimensions. The percentage agreement with previously used outcome measures ranged between 52.6 and 80.0%, the kappa values between 0.120 and 0.594. A moderate accordance (kappa value: 0.495) was found with a Clinical Global Impression (CGI) severity score of three or less. The results indicate a high descriptive validity of the symptom-severity component of the proposed remission definition. However, the new criteria differ partially from previously used outcome measures. This aspect should be considered in the interpretation of clinical trials. | 18,763,221 |
[Contrast enhanced endosonography for improving differential diagnosis between chronic pancreatitis and pancreatic cancer]. | The aim of this study was to evaluate contrast-enhanced endosonography as a method for improving the differentiation between chronic focal pancreatitis and ductal pancreatic cancer, based on perfusion characteristics of the microcirculation. In 194 patients [75 women, 119 men; age: 64 +/- 11 years] with chronic pancreatitis (n = 73) or pancreatic cancer (n = 121), pancreatic lesions were examined by conventional endoscopic B-mode ultrasound, power Doppler ultrasound and contrast-enhanced power mode, using the following criteria for malignant lesions: no detectable vascularization with conventional power Doppler scanning, irregular appearance of arterial vessels over a short distance using contrast-enhanced technique and no detection of venous vessels inside the lesion. A malignant lesion was assumed to be present if all criteria were detectable. The criteria of chronic pancreatitis without neoplasia were defined as no detectable vascularization before injection, regular appearance of vessels over a distance of at least 20 mm after injection of the contrast medium and detection of arterial and venous vessels. The gold standard was the histological diagnosis by endoscopic ultrasound (EUS)-guided fine needle aspiration cytology or operation. Using conventional EUS the diagnosis was correct in 96 of 121 patients with pancreatic cancer (sensitivity 79.3 %; 95% confindence interval 71 - 85.2%) and in 60 of 73 patients with chronic pancreatitis (specificity 82.2 % [71.5 - 90.2%]). Using contrast-enhanced EUS malignant pancreatic lesions were correctly diagnosed in 111 of 121 patients, thus increasing sensitivity to 91.7 % (85.3 - 96%). In 70 of 73 patients chronic inflammatory pancreatitis was correctly diagnosed (specificity 95.9 % [88.5 - 99,1%]) . Contrast-enhanced endoscopic ultrasound improves the differentiation between chronic pancreatitis and pancreatic carcinoma. | 18,763,228 |
Rapid and sensitive analysis of multiple bioactive constituents in Compound Danshen preparations using LC-ESI-TOF-MS. | By fully optimizing the separation and analytical conditions, a rapid-resolution LC (RRLC, 1.8 microm particle size) coupled with TOF-MS method was developed and validated for multiple compounds analysis of traditional Chinese medicinal compound preparations (TCMCPs). As a typical example, determination of Compound Danshen preparations (CDPs, mainly comprising Salvia miltiorrhiza and Panax notoginseng), was improved on three groups of bioactive constituents (phenolic acids, diterpenoids, and saponins). LODs down to 1.2 pg, permitting very good separation of 20 analytes and 3 internal standards (ISs) in 17 min, represented an approximate five-fold reduction of time compared to conventional HPLC. Unequivocal identification of target compounds in CDPs was based on accurate mass measurement of ions, and comparison of retention performance with available standards. Quantitation was carried out using the narrow window extracted ion chromatograms (XICs) of each compound with an interference-free baseline (using a +/-0.02 Da window) yielding good linearity of response (r(2) >0.9940), and excellent precision of retention time (t(R)) both interday (RSD, 0.01-0.19%) and intraday (RSD, 0.02-1.08%). The acceptable recoveries obtained were in the range of 77.69-113.8%. The results demonstrated the robustness and applicability of RRLC-TOF-MS for multicomponents analysis in TCMCPs with diverse chemical compositions and properties. | 18,763,250 |
The panel of egg allergens, Gal d 1-Gal d 5: Their improved purification and characterization. | Egg proteins represent one of the most important sources evoking food allergic reactions. In order to improve allergy diagnosis, purified and well-characterized proteins are needed. Although the egg white allergens Gal d 1, 2, 3 and 4 (ovomucoid, ovalbumin, ovotransferrin, and lysozyme) are commercially available, these preparations contain impurities, which affect exact in vitro diagnosis. The aim of the present study was to set up further purification protocols and to extend the characterization of the physicochemical and immunological properties of the final batches. The egg white allergens Gal d 1-4 were purified from commercial preparations, whereas Gal d 5 (alpha-livetin) was purified from egg yolk. The final batches of Gal d 1-5 consisted of a range of isoforms with defined tertiary structure. In addition, the IgE binding capacity of the purified egg allergens was tested using allergic patients' sera. The allergen batches will be further used to set up allergen specific diagnostic assays and to screen a larger collection of patients' sera. | 18,763,254 |
Real-time, on-line monitoring of organic chemical reactions using extractive electrospray ionization tandem mass spectrometry. | Extractive electrospray ionization mass spectrometry (EESI-MS) for real-time monitoring of organic chemical reactions was demonstrated for a well-established pharmaceutical process reaction and a widely used acetylation reaction in the presence of a nucleophilic catalyst, 4-dimethylaminopyridine (4-DMAP). EESI-MS provides real-time information that allows us to determine the optimum time for terminating the reaction based on the relative intensities of the precursors and products. In addition, tandem mass spectrometric (MS/MS) analysis via EESI-MS permits on-line validation of proposed reaction intermediates. The simplicity and rapid response of EESI-MS make it a valuable technique for on-line characterization and full control of chemical and pharmaceutical reactions, resulting in maximized product yield and minimized environmental costs. | 18,763,264 |
Urinary metabolic profile of 19-norsteroids in humans: glucuronide and sulphate conjugates after oral administration of 19-nor-4-androstenediol. | 19-Nor-4-androstenediol (NOL) is a prohormone of nandrolone (ND). Both substances are included in the WADA List of Prohibited Classes of Substances and their administration is determined by the presence of 19-norandrosterone (NA) with the urinary threshold concentration of 2 ng mL(-1). Routine analytical procedures allow the determination of NA excreted free and conjugated with glucuronic acid, but amounts of ND and NOL metabolites are also excreted in the sulphate fraction. The aim of this study is to determine the urinary metabolic profile after oral administration of a nutritional supplement containing NOL. Urine samples were collected up to 96 h following supplement administration and were extracted to obtain separately three metabolic fractions: free, glucuronide and sulphate. Extraction with tert-butyl methyl ether was performed after the hydrolysis steps and trimethylsilyl derivatives were analyzed by gas chromatography/mass spectrometry (GC/MS). After oral administration of NOL, the main metabolites detected were NA and noretiocholanolone (NE) in the glucuronide and sulphate fractions. The relative abundances of each metabolite in each fraction fluctuate with time; a few hours after administration the main metabolite was NA glucuronide whereas in the last sample (4 days after administration) the main metabolite was the NA sulphate and the second was the NE glucuronide. During the studied period almost half of the dose was excreted and the main metabolites were still found in urine after 96 h. Norepiandrosterone and norepietiocholanolone were also detected only in the sulphate fraction. Our results suggest that sulphate metabolites should be taken into consideration in order to increase the retrospectivity in the detection of 19-norsteroids after oral administration. | 18,763,272 |
Treatment of polycystic liver disease with resection-fenestration and a new classification. | To evaluate outcomes in patients with autosomal dominant polycyst liver disease (APLD) treated by combined hepatic resection and fenestration. A new classification was recommended to presume postoperative complications and long outcome of patients. Twenty-one patients with APLD were treated by a combined hepatic resection and fenestration technique. All patients were reviewed retrospectively, and clinical symptoms, performance status and morbidity were recorded. A new classification of APLD is recommended here. All patients were discharged when free of symptoms. The mean follow-up time was 55.7 mo and three patients had a recurrence of symptoms at 81, 68 and 43 mo after operation, respectively. The overall morbidity rate was 76.2%. Two patients with Type B-II and Type B-I developed biliary leakage. Four patients had severe ascites, including three with Type B-III and one with Type B-II. Nine patients had pleural effusion, including one with Type A-I; one with Type B-I; five with Type B-II; one with Type A-III and one with Type B-III. Three patients with Type B had recurrence of symptoms, while none with Type A had severe complications. Combined hepatic resection and fenestration is an acceptable procedure for treatment of APLD. According to our classification, postoperative complications and long outcome can be predicted before surgery. | 18,763,291 |
Preliminary studies on the chemical characterization and antioxidant properties of acidic polysaccharides from Sargassum fusiforme. | In order to investigate the antioxidant properties of the polysaccharides from the brown alga Sargassum fusiforme, the crude polysaccharides from S. fusiforme (SFPS) were extracted in hot water, and the lipid peroxidation inhibition assay exhibited that SFPS possessed a potential antioxidant activity. Hence, two purely polymeric fractions, SFPS-1 and SFPS-2 were isolated by the column of DEAE (2-diethylaminoethanol)-Sepharose Fast Flow, with their molecular weights of 51.4 and 30.3 kDa determined by high performance gel permeation chromatography (HPGPC). They were preliminarily characterized using chemical analysis in combination of infrared (IR) and nuclear magnetic resonance (NMR) spectroscopies and found to contain large amounts of uronic acids and beta-glycosidical linkages. The antioxidant activities of these two SFPS fractions were evaluated using superoxide and hydroxyl radical-scavenging assays. The results show that the antioxidant ability of SFPS-2 was higher than that of SFPS-1, probably correlating with the molecular weight and uronic acid content. | 18,763,305 |
Using Google Earth as an innovative tool for community mapping. | Maps are used to track diseases and illustrate the social context of health problems. However, commercial mapping software requires special training. This article illustrates how nonspecialists used Google Earth, a free program, to create community maps. The Bronx, New York, is characterized by high levels of obesity and diabetes. Residents and medical students measured the variety and quality of food and exercise sources around a residency training clinic and a student-run free clinic, using Google Earth to create maps with minimal assistance. Locations were identified using street addresses or simply by pointing to them on a map. Maps can be shared via e-mail, viewed online with Google Earth or Google Maps, and the data can be incorporated into other mapping software. | 18,763,409 |
Maternal obesity and risk of infant death based on Florida birth records for 2004. | The purpose of this study was to assess the relationship between pre-pregnancy maternal obesity and risk of infant death. In March 2004, maternal height and pre-pregnancy weight were added to the data collected on the Florida birth certificate. Using birth records linked to infant deaths, these data were used to assess the relationship between pre-pregnancy maternal obesity, as measured by body mass index, and infant death. Pre-pregnancy maternal obesity was associated with increased odds of infant death. The increased risk was found with and without adjustments for maternal race, marital status, age, education, trimester prenatal care began, first birth, and tobacco use. There is a substantial and significant association between pre-pregnancy maternal obesity and infant death. | 18,763,411 |
Receiver operating characteristics for the brief symptom inventory depression, paranoid ideation, and psychoticism scales in a large sample of clinical inpatients. | A commonly used screening tool for psychopathology, the Brief Symptom Inventory, provides normative data for assessing current mental functioning across multiple domains. Using data from 654 psychiatric inpatients, receiver operating characteristic (ROC) analyses were conducted for three scales, Depression, Paranoid Ideation, and Psychoticism. t ratios identified significant group differences on the Depression scale between patients diagnosed with or without depression but no differences on the Paranoid Ideation and Psychoticism scales between patients diagnosed with or without schizophrenia. Area under the curve for Depression was .65, indicating that the scale improved diagnostic prediction somewhat beyond chance; for Paranoid Ideation, the area was .52 and for Psychoticism, the area was .53, indicating that these two scales did not significantly improve diagnostic prediction beyond chance. | 18,763,438 |
Attractive but guilty: deliberation and the physical attractiveness bias. | The current study examined the effect of jury deliberation on the tendency for mock jurors to find attractive defendants guilty less often. It was expected that there would be an interaction between group deliberation (yes or no) and defendant's appearance (plain-looking or attractive). It was hypothesized that mock jurors who did not deliberate would be more likely to find a plain-looking defendant guilty and that deliberation would mitigate this effect. The study was a 2 x 2 between-subjects factorial design. Participants were assigned randomly to one of four conditions: attractive defendant/deliberation, attractive defendant/no deliberation, plain-looking defendant/deliberation, and plain-looking defendant/no deliberation. A total of 172 undergraduates from a small, rural college in Vermont contributed to this study: mock jurors were 70 men and 52 women, ages ranged from 18 to 52 years (M=20.5, SD=4.9). The hypothesis was supported. Mock jurors who did not deliberate were more likely to find the plain-looking defendant guilty, whereas mock jurors who deliberated were more likely to find the attractive defendant guilty. | 18,763,443 |
Women and suicide in Islamic sub-Saharan Africa. | Research on suicide among Islamic women in sub-Saharan Africa was reviewed. The few reports available do not specify the ethnicity and religious affiliation of the cases, making interpretation of the reports difficult. | 18,763,444 |
Insubordination and genius: Galileo, Darwin, Pasteur, Einstein, and Pauling. | This essay examines the lives of five great scientists who contributed enormously to mankind. Although their lives were vastly different, they all trod a final common pathway in securing scientific breakthroughs. These were stubborn, egotistical, tenacious, work-oriented people who could not be deterred by obstacles of any sort. They exemplify the unbreakable spirit required to achieve greatness. A surprising finding is the extent of hostility they all aroused from closed-minded people in society who were upset by the implications of their new ideas. It is hoped that this essay will help to stiffen the resolve of creative men and women who can expect to confront fervent opposition from others in society regardless of the value of their discoveries. | 18,763,453 |
Skin conductance as an indicator of anticipated concealed knowledge. | The present study investigated the effects of anticipation on skin conductance while participants were answering a set of questions which included one of concealed knowledge. Two experiments were conducted. In Exp. 1, 26 participants completed one experimental session. Each participant was asked to choose one two-digit number from 10 to 99 and was presented 19 other randomly generated two-digit numbers. The list of numbers was then presented to the participant on a computer screen, with a 60-sec. interval occurring every two questions. The participant-selected number was defined as the target question which was randomly placed within the 4th to 17th item of 20 questions stated as follows: "Is your selected number?" The participant was asked to answer "No" to all questions. The skin-conductance response to each question was measured. In Exp. 2, the experimental procedure was the same as that in Exp. 1 except each participant first answered 10 nontarget questions, then answered a target question with the participant's selected number, and then answered another 10 nontarget questions. There were a total of 21 questions. Analysis indicated participants in both experiments generated the highest mean skin conductance while answering the target questions, followed by lower amplitudes to questions prior to and after the target question. The skin-conductance response pattern can be used to identify the psychological process of anticipation of concealed information. | 18,763,466 |
[Ionic chemistry in snowpits from Yamzhog Yumco Basion]. | During August and September, 2006, a total of 50 samples had been collected from three different snowpits at the Yamzhog Yumco Basion in the south of the Tibetan Plateau. All samples were analyzed for major cations (Na+, NH4+, K+, Ca2+ and Mg2+), anions (Cl-, SO4(2-) and NO3-) and stable oxygen isotope ratio. The results of analyses show that the three snowpits represent accordant chemical characteristics, with NO3- (16.1-187.2 microg x L(-1), averaging at 93.7 microg x L(-1)) and Ca2+ (19.0-236.7 microg x L(-1), averaging at 81.0 microg x L(-1)) being the highest concentration of anions and cations respectively. Compared with data from other representative sites, major ion concentrations in the Yamzhog Yumco Basion accord with those in the south of the plateau, but they differ much from those in the north of th eplateau. Remarkable variabilities of major ion concentrations from monsoon period to non-monsoon period are demonstrated. Ion concentrations of NO3-, NH4+ increase 30%-40% in monsoon period due to the influences of vegetation, live-stock, anthropogenic activity and thunderstorm, whilst the concentrations of crustal source ions, such as Ca2+, Mg2+ reduce 80% due to decrease of dust and strong wind from the north of the plateau and crustal aerosols being washed out of the atmosphere by heavy precipitation during the monsoon period. Variation of ion concentrations are also impacted by elevation and post-deposition process, with Ca2+, Mg2+ increasing with a decrease in elevation and SO4(2-), NO3- decrease with an increase in elevation and the influence of post-deposition. | 18,763,489 |
[Effect and mechanism of heavy metal stabilization treatment of sediment in Jinshan Lake]. | The heavy metal stabilization treatment (by mixture of CaO, CaO2, CaO and CaO2) of sediment in Jinshan Lake were investigated through soil column experiment, including the transport and transformation of heavy metal in sediment after stabilization, and the mechanism of heavy metal stabilization treatment technology. In the simulated acid rain experiment under a pH of 2.9, Zn in the sediment stabilized by CaO, CaO+ CaO2, CaO2, respectively, transferred to the third layer with the first layer's migrating quantities of 96, 97 and 93 mg/kg, while in another experiment under a pH of 5.0, Zn transferred to the third layer with the first layer's migrating quantities of 87, 90 and 89 mg/kg, respectively. In the blank experiments under pH 2.9 and 5.0, Zn transferred to the sixth and fifth layer with the first layer migrating quantities of 128 and 112 mg/kg, respectively. The above results were concluded to be: 1) both migrating velocity and first layer's migrating quantity of Zn decreased in stabilized sediment; 2) the three tested ways could reduce it migrating capability in soil; 3) pH of leached solution could affect the migrating capability of Zn and high Ph would lead to the decrease of Zn in soil. For Ni and Cd, the similar conclusion could also be gained. The results of metal transporting mechanism experiments with CaO, CaO + CaO2, CaO2 showed that: 1) pH of the sediment increased from 6.76 to 8.33, 8.15 and 8.21; 2) TOC content decreased with a range of 5%, 10.9% and 13.1%; 3) fixedness part contents of Zn, Ni and Cd increased 10.6%, 1.7% and 4.5%, respectively, which is the important reason leading to the decrease of metal transporting capability. The transformation proportion of heavy metal from labilization to stabilization showed that the stabilization capability of heavy metal followed the sequence: Zn > Cd > Ni. | 18,763,527 |
[Preparation of Cu/ZrO2/S2O8(2-)/gamma-Al2O3 solid acid catalyst and its catalytic activity to selective reduction of NO]. | Cu/ZrO2/S2O8(2-)/gamma-Al2O3 solid acid catalyst was prepared by loading of (NH4)2S2O8, ZrOCl2, and Cu(NO3)2 onto gamma-Al2O3 step by step, which was obtained from calcining of pseudoboehmite. The catalytic property of Cu/ZrO2/S2O8(2-)/gamma-Al2O3 on the selective reduction of NO by C3H6 in excess oxygen was investigated. The relationship between the structure and the catalytic property of Cu/ZrO2/S2O8(2-)/gamma-Al2O3 catalyst was also explored by means of SEM, XRD, Py-IR and TPR. The experimental results of catalytic activity of the title catalyst indicated that the maximum conversion rate of NO could reach 82.9% in the absence of water and was up to 80.2% even in the presence of 10% water vapor. The results of the structural characterization toward the catalyst showed that S2O8(2-) and ZrO2 could restrain the sinteration of gamma-Al2O3 particles and the formation of CuAl2O4 spinelle, and also facilitate the formation of new acidic sites (Brönsted acid) and the enhance of the acidity on the surface of the catalyst. In addition, ZrO2 could increase the reducibility of Cu on the catalyst. Consequently, the catalytic activity and hydrothermal stability of the catalyst were improved effectively. | 18,763,532 |
Shallow groundwater nitrogen responses to different land use managements in the riparian zone of Yuqiao Reservoir in North China. | This field study investigated the nitrogen concentrations in the shallow groundwater from an ephemeral stream and four land uses: cropland, two-year restored (2 yr) and five-years restored (5 yr) woodlands, fishponds, and the nitrogen flux in the riparian zone of Yuqiao Reservoir. The groundwater nitrate-N concentrations in cropland were the highest among the four land uses. Total dissolved nitrogen (TDN) and nitrate-N concentrations in the 2 yr woodland were significantly (p < 0.05) higher than in 5 yr woodland. The lowest nitrogen concentrations were detected in fishponds. Nitrate-N was the main form in cropland and 2 yr woodland, whereas both nitrate-N and dissolved organic nitrogen (DON) were the main species in 5 yr woodland and fishponds. But, ammonium-N was the main form in the ephemeral stream. During the rainy season, the groundwater flow with dissolved nitrogen drains from upland into the reservoir along the hydraulic gradient. The woodland between the cropland and reservoir could act as a buffer to retain shallow groundwater nitrogen. The dominant form of ammonium-N in the groundwater TDN pool in ephemeral stream indicated that nitrogen from the village and orchard in upland flowed into the reservoir via subsurface flow. The fishpond was not an important pollution source for nitrogen transfer via shallow groundwater. | 18,763,557 |
Patient rehabilitation following lower limb amputation. | Patient rehabilitation following lower limb amputation is essential to provide optimum patient outcomes and to improve the amputee's quality of life. The age of the patient and the stump length or level of amputation emerge as dominant factors affecting the outcome of rehabilitation. A variety of outcome measures are available to assess the patient's rehabilitative potential to maximise functional ability. This article focuses on the factors affecting rehabilitation, outcome measures to assess rehabilitative potential and the nurse's role in providing care for patients following lower limb amputation. | 18,763,548 |
[Peculiarities of stress-reactivity of hypothalamo-pituitary-adrenal system in prenatally stressed rats exposed to dexamethasone]. | The protective effect of dexamethasone, a synthetic agonist of glucocorticoids, on the functional activity of hypothalamo-pituitary-adrenal system (HPAS) in adult offspring in both genders whose mothers were subject to immobilization stress in last trimester of pregnancy, has been studied. Dexamethasone treatment prior to stressing pregnant rats prevented the manifestations of injuring effect of prenatal stress on HPAS activity in adult male offspring. The post-stressor changes in hypothalamic noradrenaline content and corticosterone level in blood plasma, as well as GABAA and GABA, receptors activity, did not differ from normal indices. In prenatally stressed female rats no preventive effect of dexamethasone has been reported. The results of investigations suggest the pathogenetic role of increased production of glucocorticoids in mediating the mechanisms of prenatal stress effects in gender-related functional disorders of HPAS. They demonstrate the possibility of pharmacological prevention of some congenital forms of neuroendocrine pathology and determine the necessity of a gender approach when developing preventive strategies. | 18,763,576 |
[Age-related aspects of intestinal microflora and the intestinal immune system]. | The importance of influence of microorganisms on human health has been recognized for years. Vast amount of data has been collected regarding interaction of intestinal microflora and elements of gut immune system. Novel technologies are offering new insights into bi-directional host-flora exchange along mucosal surfaces, one of the largest interfaces of human organism. Gut is constantly being colonized through our life, therefore, mucosal immune responses require capacity to resist pathogenic bacteria. Yet gut bacterial community has a collective metabolic activity equal to a virtual organ, and the interplay between food, host cells and microbes is indispensable for shaping both innate and adaptive immunity. Age-related changes of gut microflora are well recognized, however, little is known about the feedback effect. We hypothesize that altered intestinal microflora influences mucosal immunity what in turn promotes changes on organismic level leading to further compositional and functional shifts in the microbiota. The aim of this review is to analyze current literature on the impact of such feedback. Understanding this vicious circle will ultimately lead us to better managing of number of infectious, inflammatory and neoplastic disease processes. | 18,763,586 |
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